sort by

217 publications mentioning hsa-mir-140 (showing top 100)

Open access articles that are associated with the species Homo sapiens and mention the gene name mir-140. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 403
Moreover, we highlight a new role for TGF-β in OA chondrocytes as a down-regulator of miR-140 expression, resulting in increased expression of miR-140 target genes, thus contributing to this disease process. [score:12]
NFAT5 could indirectly contribute to the down-regulation of miR-140 by up -regulating the expression of TGF-β, which in turn inhibits miR-140 expression. [score:12]
Data demonstrated (Figure  5C) that the increased expression of miR-140 following stimulation by ionomycin and NaCl resulted in decreased expression of IGFBP5, and the TGF-β -induced decrease in miR-140 led to an increased expression of IGFBP5, indicating that a change in miR-140 expression was reflected on its target gene. [score:11]
Because of its role in inhibiting key factors involved in OA pathophysiology and its down-regulation in OA cartilage, understanding the transcriptional regulation of miR-140 in this pathological condition is of great importance and could open up new therapeutic avenues targeting this disease. [score:11]
The up-regulation of WWP2/miR-140 under hypertonic conditions could occur via the transcription factor Sox9, as WWP2 and miR-140 were reported to be co-expressed and activated by Sox9 [33] and Sox9 is up-regulated by osmotic stress in human chondrocytes [41]. [score:9]
In OA chondrocytes, the increased expression of TGF-β would activate SMAD3 phosphorylation, thus directly inhibiting miR-140 as well as indirectly down -regulating miR-140 by interfering with the translocation of NFAT3. [score:8]
The -195 bp CAGA mutation (Figure  5G) resulted in a significant increase in basal (P ≤0.003) and TGF-β -induced (P ≤0.005) expression, suggesting its involvement in the negative regulation of miR-140 by TGF-β through the inhibitory action of SMAD3. [score:7]
Effect of inhibiting SMAD3 phosphorylation following incubation of osteoarthritic chondrocytes (n = 8) without (control) or with the specific SMAD3 phosphorylation inhibitor SIS3 on the C) WWP2 and D) miR-140 expression. [score:7]
Of importance, miR-140 expression is significantly decreased in human OA chondrocytes [5, 6], thus favouring an increased expression of its target genes and consequently a role in cartilage degradation. [score:7]
NFAT5, activated under hypertonic stress, up-regulates WWP2 and miR-140 expression. [score:6]
NFAT5, activated under hypertonic stress, up-regulates WWP2 and miR-140 expression. [score:6]
Additional experiments were performed to determine the expression level of a known miR-140 direct target, IGFBP5. [score:6]
This study reveals another pathway by which TGF-β affects OA chondrocytes: as a down-regulator of miR-140 expression, not only by activating SMAD3 but also by interfering with the translocation of NFAT3. [score:6]
We also identify a regulatory sequence located directly upstream of the pre-miR-140 and demonstrate the direct involvement of NFAT3 and SMAD3 on the miR-140 regulatory sequence sites as well as the indirect effect of NFAT5, possibly acting through WWP2 and TGF-β. [score:6]
Our previous study in human chondrocytes [5] and those of others in mouse cells [6, 8] identified target genes down-regulated by miR-140 that are important in the OA cartilage process. [score:6]
Besides the direct role of TGF-β on miR-140 regulation, it is also known to regulate targets of miR-140, such as IGFBP-5[5] and SMAD3[51]. [score:6]
Together, these results indicate that the TGF-β -induced miR-140 down-regulation is the result of SMAD3 activation and that NFAT3 regulates miR-140 directly, likely at the rsmiR-140 level. [score:6]
In turn, the effects of these factors on miR-140 were translated into the cells and impacted a known direct miR-140 target, IGFBP5. [score:6]
Of interest is the opposite direct regulation of miR-140 by NFAT3 (activator) and SMAD3 (inhibitor). [score:5]
As illustrated in Figure  5A and B, ionomycin significantly increased (P ≤0.05) miR-140 but not WWP2 expression, while NaCl increased both WWP2 and miR-140 expression levels but significance was reached only for WWP2 (P ≤0.03). [score:5]
While miR-140-5p was shown to target several genes involved in OA, miR-140-3p has been reported to target dynamin 1, which plays a role in the central nervous system [16] and the nuclear factor kappa B (NF-κB) co-activator nuclear receptor-interacting protein 1 [17]. [score:5]
Differential expression levels of miR-140 and WWP2We previously reported that miR-140-5p expression was significantly reduced in human OA chondrocytes [5]. [score:5]
Here, we show that, in an isotonic environment, NFAT5 could indirectly down-regulate miR-140 through the stimulation of TGF-β and subsequent activation of SMAD3. [score:5]
This study also shows the importance of TGF-β as a factor implicated in the decreased miR-140 expression in human OA chondrocytes, thus contributing to the progression of this disease. [score:5]
miRNA, microRNA; TGF-β, transforming growth factor β. In summary, this study is the first to show the important direct roles of NFAT3 and SMAD3 and the indirect role of NFAT5 in miR-140 expression. [score:5]
Data showed a pattern similar to that of the silenced SMAD3; WWP2 expression was not affected (Figure  3C) and miR-140 expression was significantly increased (P ≤0.003) (Figure  3D). [score:5]
Effect of C) TGF-β on the ionomycin -induced expression of miR-140 and of D) ionomycin on the TGF-β -induced expression of miR-140. [score:5]
However, as TGF-β is increased in OA but the expression of NFAT3 is similar in normal and OA (data not shown), the negative regulation of miR-140 levels by TGF-β/SMAD3 would prevail over the positive regulation by NFAT3 and would account for the decreased miRNA in these cells. [score:5]
Expression (number of molecules of the target gene/number of molecules of the housekeeping gene) of the intronic miRNAs A) miR-140-5p, B) miR-140-3p, and C) their host gene WWP2, of D) miR-33a and E) its host gene SREBF2, of F) miR-151 and G) its host gene PTK2/FAK in human normal (n = 6) and osteoarthritic (OA) (n = 6) chondrocytes. [score:5]
These findings indicate that the reduced expression of miR-140 in OA chondrocytes is not due to a general processing and likely results from an additional level of regulation specifically directed at this miRNA. [score:5]
Effect of silencing (siRNA) the expression of MAZ, NMP4, NFAT1-5, and SMAD3 on A) WWP2 and B) miR-140 expression in human osteoarthritic chondrocytes (n = 7 to 10). [score:5]
This study also identifies NFAT5 as an indirect regulator of miR-140 expression. [score:5]
Mutation of the NFAT site (Figure  5F) significantly decreased basal (P ≤0.0001) as well as the ionomycin -induced (P ≤0.0001) expression, indicating the involvement of this site in the positive regulation of miR-140 by NFAT3. [score:5]
TGF-β will also indirectly down-regulate miR-140 by interfering with the translocation of NFAT3. [score:5]
It is possible that the increased expression of miR-140 caused by NFAT5 under hypertonic conditions results in part from increased expression of its host gene WWP2. [score:5]
Data from this study support the hypothesis that miR-140 expression could be regulated at different levels under normal and OA conditions (Figure  8). [score:4]
In the Yang et al. article [33], however, there are no results showing that the expression of WWP2-C is differentially regulated from that of miR-140. [score:4]
We have identified rsmiR-140 as a regulatory sequence for miR-140 expression independently of its host gene. [score:4]
Identification of NFAT3 and SMAD3 as regulators of miR-140 expression independent of WWP2. [score:4]
Differential regulation between a miRNA and its host gene may not be a rare event as we have also noted that miR-151 expression, like that of miR-140, is decreased in OA independently of its host gene. [score:4]
The effect of increasing calcium flux (ionomycin), hypertonic stress (NaCl) and TGF-β on A) WWP2, B) miR-140 and C) IGFBP5 expression in human osteoarthritic chondrocytes (n = 7 to 12), and on D) the miR-140 regulatory sequence (rsmiR-140) in SW1353 cells (n = 6 to 9). [score:4]
In normal human chondrocytes, mechano-transduction triggers calcium signaling and the subsequent translocation of NFAT3 to the nucleus, where it will up-regulate miR-140. [score:4]
Identification of NFAT3 and SMAD3 as regulators of miR-140 expression independent of WWP2The rsmiR-140 sequence has several potential binding sites for transcription factors, such as NMP4 (CAAAAA), MAZ (GAGAGA), NFAT (GGAAA) and SMAD3 (CAGA, TTGGTGTTGG) (Figure  2A). [score:4]
In contrast to miR-140, the expression of WWP2 was similar in both normal and OA cells, suggesting that miR-140 has an additional level of regulation. [score:4]
The differential expression levels of WWP2 and miR-140 in OA chondrocytes [5, 6] led us to believe that this miRNA was controlled by intronic regulatory sequences in addition to the WWP2 promoter. [score:4]
Although the expression levels of both miR-140 and miR-151 are decreased in OA, their regulation is likely the result of different factors. [score:4]
In normal cells, mechano-transduction triggers calcium signaling [52, 53] and translocation of NFAT3 to the nucleus, where it will up-regulate miR-140. [score:4]
Other evidence of differential regulation was shown in zebrafish [29] in which miR-140 and WWP2 were suggested to play distinct roles in cartilage development, as the separate knockdown of WWP2 and miR-140 caused different effects. [score:4]
To examine whether these factors could be responsible for the differential regulation of miR-140 and WWP2, their expression was silenced in OA chondrocytes and the miR-140 and WWP2 levels were determined (Figure  3). [score:4]
Thus, TGF-β will increase SMAD3 phosphorylation and directly inhibit miR-140. [score:4]
Subsequent experiments were done using primers located in exons 4 and 5. To determine whether the differential expression level between WWP2 and miR-140 was due to a different miRNA processing in OA cells, we determined the levels of two unrelated intronic miRNAs: miR-33a (Figure  1D) present in one intron of the sterol regulatory element binding factor-2 (SREBF2) gene and miR-151 (Figure  1F), present in one intron of the protein tyrosine kinase or focal adhesion kinase (PTK2/FAK) gene. [score:3]
It is possible that this TSS is used to initiate WWP2-C transcription as miR-140 was reported to be co-expressed with WWP2-C[33]. [score:3]
Although both miR-140-5p and-3p are transcribed from the same precursor transcript pre-miR-140, they have different seed sequences and are, therefore, predicted to target different genes. [score:3]
DAPI, 4’,6-diamidino-2-phenylindole, dihydrochloride; TGF-β, transforming growth factor β. Further experiments were done to verify whether such interference affected miR-140 expression (Figure  7C, D). [score:3]
TGF-β interfered with NFAT3 translocation, and subsequently with miR-140 expression. [score:3]
All together, these results indicate that the presence of TGF-β interferes with the ionomycin -induced nuclear translocation of NFAT3 and ultimately miR-140 expression. [score:3]
miR-140 expression was determined by qPCR as above. [score:3]
Silencing NFAT3 significantly decreased (P ≤0.01) miR-140 expression without affecting WWP2, and silencing SMAD3 significantly increased (P ≤0.05) miR-140 without significantly affecting WWP2. [score:3]
miRNA, microRNA; TGF-β, transforming growth factor β. All together, these findings confirm that NFAT3 and SMAD3 affect miR-140 expression independently of WWP2. [score:3]
miR-140 decreases the expression of genes known to play detrimental roles in OA cartilage. [score:3]
Silencing NFAT5 significantly decreased (P ≤0.003) miR-140 and, to a lesser extent, WWP2 expression (P ≤0.05). [score:3]
This result agrees with our previous finding that BMP2, as opposed to TGF-β, does not significantly affect miR-140 expression [5]. [score:3]
1.883 kb of the 5’-flanking region directly upstream of pre-miR-140 (regulatory sequence miR-140 (rsmiR-140)) was cloned into the luciferase reporter vector pGL3-basic (Promega, Madison, WI, USA). [score:3]
This is the first study to provide evidence of a regulatory mechanism of miR-140 independent of WWP2, and new and differential roles for NFAT3 and SMAD3 in the OA process in the regulation of miR-140 transcription. [score:3]
DAPI, 4’,6-diamidino-2-phenylindole, dihydrochloride; TGF-β, transforming growth factor β. Further experiments were done to verify whether such interference affected miR-140 expression (Figure  7C, D). [score:3]
The intronic miR-140, present in the WW domain containing E3 ubiquitin protein ligase 2 (WWP2) gene, decreases the expression of genes that play detrimental roles in osteoarthritis (OA). [score:3]
We previously reported that miR-140-5p expression was significantly reduced in human OA chondrocytes [5]. [score:3]
miRNA, microRNA; TGF-β, transforming growth factor β. All together, these findings confirm that NFAT3 and SMAD3 affect miR-140 expression independently of WWP2. [score:3]
Differential expression levels of miR-140 and WWP2. [score:3]
Data showed (Figure  1A, B) that the expression levels of miR-140-5p and-3p were both markedly and significantly reduced in OA chondrocytes. [score:3]
Targeted deletion of miR-140 in mice resulted in age-related OA-like changes [8]. [score:3]
We report, for the first time, a differential expression between miR-140 and its host gene. [score:3]
Therefore, in osteoarthritic chondrocytes, the NFAT5 contribution will be lower and the TGF-β/SMAD3 negative regulation of miR-140 levels would prevail over the NFAT3 and NFAT5 positive regulation and account for the decrease in this miRNA in these cells. [score:3]
Here, we followed this by comparing its expression to that of miR-140-3p, and their host gene, WWP2, in normal and OA human chondrocytes. [score:3]
Subsequent experiments were done using primers located in exons 4 and 5. To determine whether the differential expression level between WWP2 and miR-140 was due to a different miRNA processing in OA cells, we determined the levels of two unrelated intronic miRNAs: miR-33a (Figure  1D) present in one intron of the sterol regulatory element binding factor-2 (SREBF2) gene and miR-151 (Figure  1F), present in one intron of the protein tyrosine kinase or focal adhesion kinase (PTK2/FAK) gene. [score:3]
Effect of nuclear translocation on miR-140 expression. [score:3]
Binding sites of the miR-140 regulatory sequence (rsmiR-140) were identified by mutagenesis and chromatin immunoprecipitation (ChIP) in OA chondrocytes. [score:2]
Silencing NFAT3 (P ≤0.01) and SMAD3 (P ≤0.05) differentially regulated miR-140 independently of WWP2. [score:2]
As the expression level of miR-140 is significantly decreased in human OA chondrocytes, we investigated its regulation in those cells. [score:2]
We further examined whether the regulation by NFAT3, NFAT5 and SMAD3 of miR-140 occurred at the level of rsmiR-140. [score:2]
Identification of an intronic regulatory sequence upstream of pre-miR-140. [score:2]
The arrows delineate the DNA sequence upstream of the pre-miR-140 (shown between the diagonal lines) that was cloned into the pGL3-basic vector and identified as miR-140 regulatory sequence (rsmiR-140) with the location of potential transcription factor binding sites. [score:2]
To determine if such was the case for miR-140 and WWP2, we cloned 1.883 kb and 1.153 kb (Figure  2A) of the sequence located directly upstream of the pre-miR-140 [GenBank:NC_000016]. [score:2]
Both plasmids promoted similar transcriptional activity (Figure  2B), indicating the presence of regulatory elements in the sequence upstream of pre-miR-140. [score:2]
Figure 8 Hypothesis on the regulation of miR-140 in human normal and osteoarthritic chondrocytes by TGF-β, SMAD3, NFAT3 and NFAT5. [score:2]
The addition of TGF-β during the ionomycin treatment resulted in a significant decrease (P ≤0.02) in miR-140 compared to ionomycin treatment alone, while the addition of ionomycin to the TGF-β treatment did not significantly affect the miR-140 expression level. [score:2]
Mutagenesis of rsmiR-140 and ChIP assays identified binding sites at which NFAT3 (activator) and SMAD3 (repressor) directly regulated miR-140. [score:2]
To verify that SMAD3, but not SMAD1, was involved in miR-140 regulation, the cells were treated with BMP2 (10 ng/ml); rsmiR-140 activity was not affected by this factor (data not shown). [score:2]
Cloning of the 5’-flanking region of pre-miR-140 (rsmiR-140). [score:1]
This is in agreement with a search through the miRStart database [34], which revealed two potential transcription start sites (TSS) within the 50,000 bp upstream region of the miR-140 precursor. [score:1]
As both miR-140 s are similarly decreased in OA chondrocytes, further experiments were carried out with miR-140-5p. [score:1]
Analysis of the intronic sequence has revealed the presence of two miR-140 s, miR-140-5p and miR-140-3p. [score:1]
Expression as measured by qPCR of WWP2, miR-140, IGFBP5, and TGF-β in OA control chondrocytes; rsmiR-140 activity in control cells from mutagenesis experiments; basal PCR values of NFAT3 and SMAD3 in OA control chondrocytes in ChIP experiments. [score:1]
miR-140 is found in one intron of the WW domain containing E3 ubiquitin protein ligase 2 (WWP2) gene [15]. [score:1]
However, unlike miR-140, miR-151 has not been identified in miRNA profiling of OA cartilage [30, 31], but has been associated with carcinomas [32]. [score:1]
RNA was extracted and the expression of miR-140 was measured. [score:1]
All of the previous studies done with arthritic cells and tissues used miR-140-5p. [score:1]
Click here for file Expression as measured by qPCR of WWP2, miR-140, IGFBP5, and TGF-β in OA control chondrocytes; rsmiR-140 activity in control cells from mutagenesis experiments; basal PCR values of NFAT3 and SMAD3 in OA control chondrocytes in ChIP experiments. [score:1]
Furthermore, a search through the literature has not revealed any family relationship between the two miRNAs; an in silico analysis of the 2 kb sequence located upstream of the mature miR-151 did not reveal any NFAT3 or SMAD3 consensus binding sites, as was the case with miR-140. [score:1]
The second TSS is located at position 976 bp upstream of the pre-miR-140, thus within the cloned rsmiR-140 sequence, which we have shown to be capable of promoting transcription independently of WWP2, unlike the region identified by Yang et al. [33]. [score:1]
Silencing NMP4 significantly increased WWP2 (P ≤0.05) but not miR-140, and silencing NFAT1, NFAT2, NFAT4 or MAZ did not significantly affect either miR-140 or WWP2 levels. [score:1]
A) Sequence of the miR-140 precursor (pre-miR-140) stem-loop located in intron 16 of the WWP2 gene. [score:1]
TGF-β significantly decreased (P ≤0.05) miR-140 but had no true effect on WWP2 levels. [score:1]
Silencing NFAT5 decreased both miR-140 and WWP2 (P ≤0.003 and P ≤0.05, respectively). [score:1]
Some miRNAs including miR-146 and miR-155 have been linked to arthritis pathologies, such as rheumatoid arthritis [1- 3], but miR-140, originally found in cartilage [4], has been linked more specifically to osteoarthritis (OA) [5, 6]. [score:1]
Figure 2 miR-140 sequence and activity of rsmiR-140. [score:1]
[1 to 20 of 106 sentences]
2
[+] score: 374
miR-140-5p also plays a tumor suppressor role in hepatocellular carcinoma by controlling NF-κB activity by directly regulating DNMT1 expression [19], and suppresses tumor growth and metastasis by targeting TGFBR1 and FGF9 [20]. [score:11]
In this study, we revealed that miR-140-5p is commonly down-regulated in CC, and in vitro and in vivo assays further demonstrated that miR-140-5p suppresses CC cell proliferation, migration and invasion by direct targeting IGF2BP1. [score:8]
By dividing CC patients into high and low expression of miR-140-5p according to the median level of miR-140-5p, survival analysis revealed that the median survival time was significantly longer in CC patients with higher miR-140-5p expression than that in those with lower miR-140-5p expression (Figure 1B). [score:7]
Wound healing assay showed that the over -expression/inhibitation of miR-140-5p significantly decreased/increased would healing in both C33A (Figure 3A) and HeLa (Figure 3B) cells, and transwell migration assay revealed that the over -expression/inhibitation of miR-140-5p significantly decreased/increased cell migration in both C33A and HeLa cells (Figure 3C and 3D). [score:7]
miR-140-5p directly targets and down-regulates IGF2BP1. [score:7]
In parallel, we transfected C33A and HeLa cells with a miRNA inhibitor to inhibit expression of miR-140-5p (Supplementary Figure S1A). [score:7]
To understand how miR-140-5p inhibits CC growth and metastasis, we searched potential targets of miR-140-5p by three computational algorithms (TargetScan, miRanda, and Pictar). [score:7]
These results indicated that the effects of IGF2BP1 RNA interference/over -expression were similar to that of miR-140-5p over -expression/inhibition. [score:7]
miR-140-5p expression is also reduced in non-small cell lung cancer, and it suppresses tumor growth and metastasis by targeting IGF1R [21]. [score:7]
IGF2BP1 is a direct functional target of miR-140-5p, and is involved in the miR-140-5p induced suppression of CC development. [score:7]
Figure 5 A. Targetscan program predicts that IGF2BP1 is a direct target gene of miR-140-5p. [score:6]
A. Targetscan program predicts that IGF2BP1 is a direct target gene of miR-140-5p. [score:6]
Results showed that miR-140-3p was also down-regulated in CC tissues compared with normal cervixes and significantly amplified in CC cells transfected with over -expression vector. [score:5]
qRT-PCR results of cell lines showed that compared with that in H8, miR-140-5p was down-regulated with different expression levels in C33A (0.61 ± 0.14 fold), HeLa (0.13 ± 0.01 fold), SiHa (0.35 ± 0.05 fold), CaSki (0.43 ± 0.04 fold) and ME-180 (0.02 ± 0.003 fold) (Figure 1C). [score:5]
miR-140-5p over -expression suppresses CC cell proliferation in vitro. [score:5]
H. of the effects of miR-140-5p over -expression and inhibition on IGF2BP1 protein levels in C33A and HeLa cells. [score:5]
In this study, miR-140 was constructed as over -expression vector, and miR-140 may express both miR-140-5p and miR-140-3p. [score:5]
miR-140-5p over -expression suppresses CC tumor growth and metastasis in vivo. [score:5]
Our findings described a novel role of miR-140-5p as a tumor suppressor by targeting IGF2BP1 in CC. [score:5]
Taken together, these results indicated that miR-140-5p over -expression can suppress tumor growth and metastasis in vivo. [score:5]
Of the potential targets that were predicted by all three algorithms, insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was identified as a candidate target of miR-140-5p (Figure 5A and 5B) and attracted our attention as it has been reported to be implicated in tumorigenesis [22]. [score:5]
We checked the expression of miR-140-3p in CC tissues (n=21) and unmatched normal cervixes (n=8), and in CC cells transfected with over -expression vector by qRT-PCR. [score:5]
HeLa and C33A cells were transfected with hsa-miR-140 plasmid, mock plasmid (negative control), IGF2BP1 plasmid, mock plasmid (negative control), miRNA Inhibitor, Inhibitor control (miR20000431-1-5, RiboBio, Guangzhou, China) using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) in accordance with the manufacturer's instructions. [score:5]
Kaplan-Meier method [43] was used to analyze the survival difference between the high miR-140-5p expression CC patients and the low miR-140-5p expression CC patients. [score:5]
E. qRT-PCR analysis of the effects of miR-140-5p over -expression and inhibitor on IGF2BP1 mRNA levels in C33A and HeLa cells. [score:5]
for miR-140-5p over -expression and inhibition in C33A A. and HeLa B. cells. [score:5]
However, the subsequent inhibition assays, luciferase reporter assay, and rescue assays further demonstrated that miR-140-5p exerts its tumor suppressor role in CC cells by targeting IGF2BP1. [score:4]
In addition, it has been suggested that miR-140-5p plays a role in the development of chemoresistance in human osteosarcoma and colon cancers by reduced cell proliferation through G1 and G2 phase arrest mediated in part through the suppression of HDAC4 [18]. [score:4]
Thus the in vitro assays of CC cells transfected with over -expression vector demonstrated that both miR-140-5p and miR-140-3p may act as CC suppressor. [score:4]
Transwell migration and matrigel invasion assays for miR-140-5p over -expression and inhibition in C33A C. and HeLa D. cells. [score:4]
Our data-mining based on public available CC genomic data showed that miR-140-5p was down-regulated in CC samples and negatively correlated with poor prognosis of CC patients. [score:4]
miR-140-5p directly targets IGF2BP1 in CC cells. [score:4]
In addition, the results from colony formation assay showed that over -expression of miR-140-5p significantly suppressed the potential of cell colony formation in both C33A and HeLa cells (Figure 2C). [score:4]
Furthermore, IGF2BP1 was identified as a direct functional target of miR-140-5p in CC, and it might exert its biological function by interaction with c-myc. [score:4]
These results prompted us to validate whether IGF2BP1 is the direct downstream target of miR-140-5p. [score:4]
Taken together, these results indicated that IGF2BP1 is a direct downstream target of miR-140-5p in CC cells. [score:4]
We found that miR-140-5p was down-regulated in CC samples and cell lines, and was inversely correlated with the levels of insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) in CC patients. [score:4]
IHC analysis revealed that c-MYC was increased in human CC tissues compared with that in human normal cervix (Supplementary Figure S5A), and western blot analysis showed that both the over -expression of miR-140-5p and IGF2BP1 RNA interference in C33A similarly decreased the protein expression of c-MYC (Supplementary Figure S5B). [score:4]
Figure 3Wound healing assays for miR-140-5p over -expression and inhibition in C33A A. and HeLa B. cells. [score:4]
Cellular function assays showed that over -expression of IGF2BP1 significantly rescued miR-140-5p induced inhibition of cell proliferation (Figure 7B), migration and invasion (Figure 7C and 7D) in C33A and HeLa cells. [score:4]
Down-regulation of miR-140-5p is associated with CC poor prognosis. [score:4]
In addition, we compared clinicopathological variables between CC patients with positive (n=10) and negative (21) miR-140-5p expressions, and found that a remarkably negative miR-140-5p expression was significantly associated with lymph node metastasis (Table 1). [score:4]
miR-140-5p is down-regulated in CCs and positively correlated with patient survival. [score:4]
These data mining and expression analysis results prompted us to hypothesize that miR-140-5p may be involved in the tumorigenesis of CC. [score:3]
Figure 2 A. qRT-PCR analysis of miR-140-5p expression in miR-140-5p -transfected and mock -transfected cells. [score:3]
Taken together, these data suggested that, and it is functional target of miR-140-5p. [score:3]
Results showed that miR-140-5p transfection/inhibitation dramatically decreased/increased the cells invaded across the film (Figure 3C and 3D). [score:3]
Similarly, qRT-PCR results of tissues revealed that miR-140-5p was significantly down-regulated in human CC tissues (n=21) compared with normal cervixes (n=8) (Figure 1D). [score:3]
All these previous findings suggest that miR-140-5p functions as a tumor-suppressor. [score:3]
These results prompt us to hypothesize that miR-140-5p may play a tumor-suppressor role in CC cells. [score:3]
E. Representative HE straining and in situ hybridization (ISH) analysis of miR-140-5p expression in CC tissues and in matched adjacent non-tumor specimens (n = 31). [score:3]
IGF2BP1 is involved in miR-140-5p -induced proliferation, migration and invasion inhibition in C33A and HeLa cells. [score:3]
Cellular and mo del animal experiments revealed that miR-140-5p acted as a tumor suppressor by affecting CC cell proliferation, migration, and invasion. [score:3]
A. TCGA database analysis of miR-140-5p expression in CCs (n = 307) and in normal human cervix (n = 3). [score:3]
C. The effect of miR-140-5p over -expression on the colony formation. [score:3]
However, miR-140-3p has been reported to be involved in lung cancer suppression [37– 38] and diagnosis of lung squamous cell carcinoma [39]. [score:3]
miR-140-5p inhibits CC cell migration and invasion in vitro. [score:3]
D. PI staining and FACS analysis of the effect of miR-140-5p over -expression on cell cycle progress. [score:3]
Commercial TMAs were used to analyze the expression of has-miR-140-5p in CC tissues based on ISH analysis. [score:3]
IGF2BP1 is involved in miR-140-5p -induced CC suppression. [score:3]
The relationship between miR-140-5p expression and the survival of CC patients was assessed by univariate Cox regression [42]. [score:3]
Recalling the expression levels of miR-140-5p in human CC tissues and cell lines, a statistically significant inverse correlation was observed by Spearman's correlation analysis between RNA levels of miR-140-5p and mRNA levels of IGF2BP1 in both human CC tissues (Figure 5D) and cell lines (Supplementary Figure S3B). [score:3]
org/) [47] were used to predict potential target genes of miR-140-5p. [score:3]
Figure 1 A. TCGA database analysis of miR-140-5p expression in CCs (n = 307) and in normal human cervix (n = 3). [score:3]
The biological function of miR-140-5p has been studied only in a limited number of malignant carcinomas such as breast cancer, osteosarcoma, colon cancer, hepatocellular carcinoma and non-small cell lung cancer, and all these previous findings suggested that miR-140-5p functions as a tumor-suppressor in these cancers [17– 21]. [score:3]
In breast cancer, miR-140-5p has been identified as a tumor suppressor due to the interaction with SOX2 [17]. [score:3]
Univariate Cox regression analysis of 307 CC samples revealed that decreased miR-140-5p expression was a highly significant negative risk factor (HR = 0.89, P < 0.05). [score:3]
miR-140-5p suppresses CC cell proliferation in vitro. [score:3]
To explore the possible biological significance of miR-140-5p in CC cells, we constructed stable cell lines expressing miR-140-5p from C33A and HeLa cells (Figure 2A). [score:3]
We have observed the suppression effects of miR-140-5p on proliferation, migration, and invasion of CC cells in vitro, we then examined the role of miR-140-5p on CC tumor growth and metastasis in vivo. [score:3]
Furthermore, qRT-PCR and western blot assays revealed that over -expression/inibition of miR-140-5p significantly decreased/increased the expression of IGF2BP1 mRNA (Figure 5E) and protein (Figure 5H) levels in both C33A and HeLa cells, and IHC analysis revealed that IGF2BP1 was increased in human CC tissues (17 positive samples out of 21 samples) compared with that in human normal cervixes (2 positive samples out of 8 samples) (Figure 5F, P<0.01). [score:3]
The R Limma package [41] was used to compare the expression of miR-140-5p between CC samples and normal cervical samples. [score:3]
The results showed that miR-140-5p over -expression was found to promote cell death in both C33A and HeLa cells significantly (Supplementary Figure S2). [score:3]
A. qRT-PCR analysis of miR-140-5p expression in miR-140-5p -transfected and mock -transfected cells. [score:3]
These data suggested that miR-140-5p suppresses CC cell migration and invasion in vitro. [score:3]
As expected, miR-140-5p over -expression triggered an cell cycle arrest at G0/G1 phase, and the cell proportions at S and G2/M phases in both C33A and HeLa were deceased significantly (Figure 2D). [score:3]
B. Survival analysis of miR-140-5p expression in TCGA database. [score:3]
In this study, we objected to illustrate the tumor-suppressor role of miR-140-5p in CC and elucidate the underlying molecular mechanism. [score:3]
Correlation between clinicopathological variables and miR-140-5p expression in 31 CC patients. [score:3]
The results showed that the tumors from miR-140-5p over -expressing cells were significantly smaller in tumor volume and weight than that from control cells (Figure 4A and 4B). [score:3]
The results indicated that miR-140-5p may suppress cell proliferation by inducing cell cycle arrest in CC. [score:3]
results revealed that miR-140-5p directly bound to IGF2BP1 3′ UTR by which it remarkably decreased the relative luciferase activity of IGF2BP1-3′UTR in C33A and HeLa cells, but had no effect on the mutant of IGF2BP1-3′UTR (Figure 5G). [score:2]
miR-140-5p negatively regulated the migration and invasion of CC cells in vitro. [score:2]
CCK8 and colony formation assays revealed that inhibition of miR-140-5p significantly increased cell viability (Supplementary Figure S1B) and colony formation (Supplementary Figure S1C) of C33A and HeLa cells. [score:2]
B. CCK8 assay of the effect of miR-140-5p over -expression on cell viability. [score:2]
miR-140-5p binding sites from 3′ UTR or mutant 3′ UTR of IGF2BP1were cloned into the pGL3 reporter luciferase vector (GeneChem). [score:1]
cDNAs encoding hsa-miR-140 sequences were subcloned into a pEZX-MR03 puro DNA plasmid (GeneCopoeia, MD, USA) in which a puromycin selectable marker was encoded. [score:1]
C33A and HeLa cells were transfected with specific miR vector+vector, miR vector+IGF2BP1, miR-140-5p+vector or transfected with IGF2BP1 plasmid lacking 3′UTR along with miR-140-5p. [score:1]
However, the roles and potential mechanisms of miR-140-5p in CC remain unclear. [score:1]
In conclusion, this study identified a novel miR-140-5p-IGF2BP1 axis which accounts for CC pathogenesis and has potential therapeutic value for CC treatment. [score:1]
To further illustrate the biological significance of miR-140-5p in CC cells, we investigated whether miR-140-5p could also inhibit cell migration and invasion in CC. [score:1]
We cloned IGF2BP1 3′ UTR containing putative miR-140-5p binding site into a luciferase reporter vector. [score:1]
In situ hybridization (ISH) for miRNA-140-5p. [score:1]
miR-140-5p decreases CC growth and metastasis in vivo. [score:1]
miR-140-5p -transfected C33A and HeLa cells were stained with propidium iodide (PI), and analyzed by fluorescence microscope. [score:1]
C. In vivo nude mouse mo del analysis of the effect of miR-140-5p on mouse weight implanted with C33A (injection by caudal vein). [score:1]
Figure 4 A-B. In vivo nude mouse mo del analysis of the effect of miR-140-5p on tumor growth (injection by s. c. ). [score:1]
B. The wild-type (WT) or mutant (MUT) binding sequences of miR-140-5p on IGF2BP1 3′-UTR. [score:1]
For the comparison of tumor growth, C33A-miR-140-5p and C33A-vector cells were inoculated subcutaneously into the flank of nude mice with 1 × 10 [7]cells per mouse. [score:1]
For comparison of tumor metastasis, C33A-miR-140-5p and C33A-vector cells were injected into nude mice via tail vein injection. [score:1]
To investigate whether the tumor suppressor function of miR-140-5p is mediated by IGF2BP1, C33A and HeLa cells were stably transfected with IGF2BP1 siRNA and IGF2BP1. [score:1]
Figure 7C33A and HeLa cells were transfected with specific miR vector+vector, miR vector+IGF2BP1, miR-140-5p+vector or transfected with IGF2BP1 plasmid lacking 3′UTR along with miR-140-5p. [score:1]
D. Spearman's correlation analysis between miR140-5p levels and IGF2BP1 mRNA levels in 21 CC tissues. [score:1]
To further confirm the proliferation suppression function of miR-140-5p on cervical cancer cells, we investigated the cell cycle progress of C33A and HeLa cells by flow cytometry. [score:1]
C. qRT-PCR analysis of miR-140-5p levels in one normal cervical cell line (H8) and five CC cell lines (C33A, CaSki, SiHa, HeLa, and ME-180). [score:1]
Thus though the role of miR-140-3p in CC cells is still unclear, we speculate that miR-140-3p may acts as a tumor suppressor in CC cells, and investigations will be expanded on this issue in the future. [score:1]
D. qRT-PCR analysis of miR-140-5p levels in 8 normal cervix tissues and 21 CC tissues. [score:1]
We analyzed TCGA data for miR-140-5p levels and for correlation with patient survival. [score:1]
D. Histological analysis of the effect of miR-140-5p on the tumor growth in nude mouse lung metastatic mo del. [score:1]
A-B. In vivo nude mouse mo del analysis of the effect of miR-140-5p on tumor growth (injection by s. c. ). [score:1]
Furthermore, miR-140-5p transfected C33A and HeLa cells were transfected with IGF2BP1 plasmids lacking 3′UTR (Figure 7A). [score:1]
Lung histological results showed that more cancer cells were observed in C33A-vector group than that in C33A-miR-140-5p group (Figure 4D). [score:1]
[1 to 20 of 112 sentences]
3
[+] score: 323
Other miRNAs from this paper: hsa-mir-27a, hsa-mir-215, hsa-mir-144, hsa-mir-193b
miR-140 inhibits breast or colorectal CSC survival and cancer invasive phenotype via downregulation of SOX2/9 or Smad2 [17– 21], whereas, during embryonic bone development, miR-140 drives chondrocyte cell proliferation [8, 9] by targeting HDAC4 and the subsequent transcription of Runx2 [9]. [score:9]
The gain-of- and loss-of-function studies showed that miR-140 inhibited CRC cell migratory and invasive capacities at least partially via downregulating the expression of ADAMTS5 and IGFBP5. [score:8]
In hepatocellular carcinoma (HCC), miR-140 was found to target TGFBRI and FGF9, and its overexpression could suppress HCC growth and metastasis [14]. [score:7]
The results from our group showed that ectopic expression of miR-140 in human osteosarcoma and CRC cells can induce cell cycle arrest and inhibit cell proliferation, in part through the suppression of histone deacetylase 4 (HDAC4) [13]. [score:7]
Zhai H Fesler A Ba Y Wu S Ju J Inhibition of colorectal cancer stem cell survival and invasive potential by hsa-miR-140-5p mediated suppression of Smad2 and autophagyOncotarget. [score:7]
Li W Jiang G Zhou J Wang H Gong Z Zhang Z Min K Zhu H Tan Y Down-regulation of miR-140 induces EMT and promotes invasion by targeting Slug in esophageal cancerCell Physiol Biochem. [score:6]
These findings suggest that miR-140 suppresses CRC progression and metastasis, possibly through downregulating ADAMTS5 and IGFBP5. [score:6]
Wienholds et al. [8] and Tuddenham et al. [9] reported that miR-140 was specifically expressed in cartilage tissues of zebrafish and mouse embryos, and later its downregulation was shown to play a critical role in the pathogenesis of osteoarthritis (OA) [10– 12]. [score:6]
miR-140 downregulation and ADAMTS5 and IGFBP5 overexpression contribute to the TNM stage and metastasis of CRC. [score:6]
miR-140 downregulation and ADAMTS5 or IGFBP5 overexpression were associated with the advanced TNM stage and distant metastasis of CRC. [score:6]
In summary, we experimentally prove that miR-140 inhibits CRC cell migration and invasion upon downregulating ADAMTS5 and IGFBP5. [score:6]
miR-140 expression is reduced in the CRC specimens, and its downregulation is associated with the tumor stage and metastasis. [score:6]
To knock down the endogenous miR-140, HCT116 and R KO cells were transfected with 100 nM of scrambled miRNA inhibitor or miR-140 inhibitor by lipofectamine 2000 (Invitrogen) in six-well plates (3 × 10 [5] cells/well), respectively. [score:6]
Lipofectamine 2000 (Control), scrambled miRNA inhibitor (Anti-NC) and co-transfection of miR-140 inhibitor and siRNA against ADAMTS5 (140i + siADAMTS5) or IGFBP5 (140i + siIGFBP5) were the negative controls. [score:5]
Previously we confirmed that ADAMTS5 and IGFBP5 were downregulated by miR-140 in the CRC cell lines, and miR-140 expression was decreased in the CRC specimens as compared to the normal colorectal tissues. [score:5]
The inhibition of CRC cell migration and invasion by miR-140 is achieved possibly due to the suppression of ADAMTS5 or IGFBP5 (Fig.   3). [score:5]
Together, miR-140 inhibits the capacities of migration and invasion of CRC cells in vitro, possibly through targeting of ADAMTS5 and IGFBP5. [score:5]
In this study, we revealed a novel mechanism for the inhibition of miR-140 in the CRC progression through targeting ADAMTS5 and IGFBP5. [score:5]
miR-140 inhibited esophageal cancer cell invasion by targeting slug and the subsequent epithelial-mesenchymal transition (EMT) process [16]. [score:5]
In non-small cell lung cancer (NSCLC), miR-140 can target IGF1R and monocyte to macrophage differentiation -associated (MMD) to inhibit tumor growth and metastasis [15]. [score:5]
Zhang Y Eades G Yao Y Li Q Zhou Q Estrogen receptor α signaling regulates breast tumor-initiating cells by down -regulating miR-140 which targets the transcription factor SOX2J Biol Chem. [score:5]
In accordance with our results, Zhai et al. [21] found a more progressive reduction in miR-140 in the metastatic CRC tissues than in the primary tissues, and patients with high miR-140 expression had a much longer survival time, further supporting the inhibitory effect of miR-140 on the CRC metastasis. [score:5]
To further confirm that the expressions of ADAMTS5 and IGFBP5 are indeed regulated by miR-140 in CRC cells, we transiently transfected either miR-140 mimic or negative miRNA into HCT116 or R KO cells. [score:4]
ADAMTS5 and IGFBP5 are downregulated by miR-140 in HCT116 and R KO cells. [score:4]
We found that miR-140 inhibited the protein expressions (Fig.   2c) and decreased the mRNA levels of ADAMTS5 and IGFBP5 (Fig.   2d) in both HCT116 and R KO cells compared to the negative controls. [score:4]
The endogenous miR-140 was knocked down with inhibitor in HCT116 and R KO cells using lipofectamine 2000. [score:4]
ADAMTS5 and IGFBP5 were downregulated by miR-140 at both the protein and mRNA levels in the CRC cell lines. [score:4]
Fig. 2ADAMTS5 and IGFBP5 are downregulated by miR-140 in CRC cells. [score:4]
More importantly, miR-140 downregulation was significantly associated with advanced clinical stage and distant metastasis of CRC (Table  1). [score:4]
Additionally, several studies indicated that downregulation of miR-140 can promote cancer stem cell (CSC) formation in breast cancer and CRC [17– 21]. [score:4]
Thus, miR-140 impairs the migratory and invasive capacities of CRC cells in vitro, possibly via downregulating ADAMTS5 and IGFBP5. [score:4]
The later studies performed by Miyaki et al. [10] and Tardif et al. [38] have experimentally identified that ADAMTS5 and IGFBP5 are the direct targets of miR-140 in HEK293T cells or human OA chondrocytes. [score:4]
Very interestingly, Miyaki et al. [10] and Tardif et al. [38] have experimentally confirmed that ADAMTS5 and IGFBP5 are the direct targets of miR-140 in HEK293T cells and human OA chondrocytes, respectively. [score:4]
In the current study, we confirmed that ADAMTS5 and IGFBP5 are downregulated by miR-140 in the CRC cell lines (Fig.   2). [score:4]
Li W He F Monocyte to macrophage differentiation -associated (MMD) targeted by miR-140-5p regulates tumor growth in non-small cell lung cancerBiochem Biophys Res Commun. [score:4]
miR-140 downregulation has also been verified in other solid cancers including HCC, NSCLC, and esophageal cancer [14– 16], and miR-140 is negatively associated with tumor stage and metastasis of HCC and NSCLC [14, 15]. [score:4]
In order to further elucidate the impacts of miR-140, we performed a series of knockdown experiments using miRNA inhibitors in HCT116 and R KO cells. [score:4]
Yang H Fang F Chang R Yang L MicroRNA-140-5p suppresses tumor growth and metastasis by targeting transforming growth factor β receptor 1 and fibroblast growth factor 9 in hepatocellular carcinomaHepatology. [score:4]
In the current study, we investigated the suppressive role of miR-140 in CRC progression and the correlation with downregulating ADAMTS5 and IGFBP5. [score:4]
These data indicated that ADAMTS5 and IGFBP5 expressions are regulated by miR-140 at the post-transcriptional level in the CRC cells, and this is consistent with the previous results [10, 38]. [score:4]
The expressions of ADAMTS5 and IGFBP5 mRNA were dramatically increased in CRC specimens compared with adjacent normal tissues (Fig.   4a; P < 0.05), and the expression patterns were inversely correlated with that of miR-140 (Fig.   4b). [score:4]
Li Q Yao Y Eades G Liu Z Zhang Y Zhou Q Downregulation of miR-140 promotes cancer stem cell formation in basal-like early stage breast cancerOncogene. [score:4]
All these results indicated that ADAMTS5 and IGFBP5 are downregulated by miR-140 in CRC cells. [score:4]
ADAMTS5 and IGFBP5 are inversely correlated with the expression of miR-140 and enhance the progression and metastasis of CRC. [score:3]
The correlation between miR-140 expression and clinicopathological parameters was shown in Table  1. Our results indicated that miR-140 was negatively correlated with tumor stage (P = 0.045) and metastasis (P = 0.031). [score:3]
Consistent with this, Güllü et al. [23] reported that, immunohistochemically, IGFBP5 -negative breast cancer samples have a significantly increased expression of miR-140. [score:3]
Güllü et al. [23] also found that miR-140 is overexpressed in the invasive ductal breast cancer tissues and lymph node -positive samples. [score:3]
ADAMTS5 and IGFBP5 are overexpressed in the CRC specimens and are inversely correlated with the levels of miR-140. [score:3]
These results are highly consistent with those obtained from exogenous miR-140 overexpression experiments. [score:3]
Several studies have shown that miR-140 participates in the tumor invasion and metastasis through targeting TGFBR1, FGF9, IGF1R, MMD, and Slug [14– 16]. [score:3]
There was a reverse correlation between miR-140 levels and ADAMTS5 and IGFBP5 expression in CRC tissues. [score:3]
miR-140 was significantly reduced, whereas ADAMTS5 and IGFBP5 were upregulated, in the human CRC tissues compared to the corresponding normal colorectal mucosa. [score:3]
83.2 ± 6.1 or 82.6 ± 7.9, P < 0.05; Fig.   3c), while silenced ADAMTS5 (32.9 ± 3.8) or IGFBP5 (35.8 ± 2.6) had a similar effect with miR-140 overexpression (Fig.   3c). [score:3]
We next confirmed the inhibitory effects of miR-140 on the CRC cell migration and invasion in vitro (Fig.   3). [score:3]
Co-transfections of miR-140 inhibitor and siADAMTS5 or siIGFBP5 were the negative control. [score:3]
Güllü G Peker I Haholu A Clinical significance of miR-140-5p and miR-193b expression in patients with breast cancer and relationship to IGFBP5Genet Mol Biol. [score:3]
Expression level of miR-140 was normalized by the internal control RNU6B in each sample. [score:3]
The relative expression of miR-140 was determined by qRT-PCR after normalization to the internal control, RNU6B. [score:3]
miR-140 inhibits the migratory and invasive capacities of CRC cells. [score:3]
b Correlation of ADAMTS5 and IGFBP5 and miR-140 expression was analyzed by Spearman correlation test in CRC tissues. [score:3]
Our previous study has shown that miR-140 inhibits human osteosarcoma and CRC cell growth and is also involved in the chemoresistance to methotrexate and 5-fluorouracil (5-FU) [13]. [score:3]
To more accurately verify the regulation between miR-140 and ADAMTS5 or IGFBP5, we co -transfected miR-140 inhibitor and siRNA against ADAMTS5 or IGFBP5, respectively, into the CRC cells and considered it as a negative control. [score:3]
Fig. 4ADAMTS5 and IGFBP5 are inversely correlated with the expression of miR-140 and positively correlated with the tumor stage and metastasis of CRC. [score:3]
miR-140 knockdown. [score:2]
As Fig.   3a showed, the gap was broader in the miR-140-transfection cells compared with the negative controls both in HCT116 and R KO cells, and the wound closure was also significantly inhibited by silenced ADAMTS5 or IGFBP5. [score:2]
Knockdown of miR-140 promotes the migratory and invasive capacities of CRC cells. [score:2]
We reasoned that miR-140 may influence CRC progression and be a key regulator in CRC. [score:2]
These data in the clinical specimens further prove the negative regulatory interaction of miR-140 and ADAMTS5 and IGFBP5 concluded from the in vitro experiments. [score:2]
Tardif G Hum D Pelletier JP Duval N Martel-Pelletier J Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytesBMC Musculoskelet Disord. [score:2]
microRNA-140-5p (miR-140) has been shown to be involved in cartilage development and osteoarthritis (OA) pathogenesis. [score:2]
These findings suggested that miR-140 may play a critical role in CRC development and progression. [score:2]
To determine the role of miR-140 in CRC development and progression, we evaluated the expressions of miR-140 in 60 paired CRC specimens and the corresponding normal colorectal tissues using qRT-PCR analysis. [score:2]
We found that miR-140 expression was significantly decreased in the CRC tissues compared with the normal controls (P = 0.037, Fig.   1). [score:2]
The clinical relevance of miR-140 in these tumor samples indicates that miR-140 might be a critical regulator of cancer progression. [score:2]
miR-140 might be a key regulator in CRC progression and metastasis and a potential therapeutic candidate for the treatment of CRC. [score:2]
de) has shown that the 3′-UTR of ADAMTS5 or IGFBP5 mRNA contains the putative binding sites of miR-140 (Fig.   2a). [score:1]
Our clinical observations also showed that miR-140 has inverse correlation with ADAMTS5 or IGFBP5 (Fig.   4). [score:1]
Colorectal cancer microRNA-140-5p ADAMTS5 IGFBP5 Invasion Metastasis Colorectal cancer (CRC) is one of the most common malignancies and the second most common cause of cancer deaths worldwide [1, 2]. [score:1]
Importantly, several recent studies have revealed the functions of miR-140 in tumorigenesis. [score:1]
Wolfson B Eades G Zhou Q Roles of microRNA-140 in stem cell -associated early stage breast cancerWorld J Stem Cells. [score:1]
Our interest in miR-140 was due to our previous study that indicates its effects on CRC cell proliferation and chemoresistance [13]. [score:1]
Miyaki S Sato T Inoue A Otsuki S Ito Y Yokoyama S Kato Y Takemoto F Nakasa T Yamashita S Takada S Lotz H Ueno-Kudo MK Asahara H MicroRNA-140 plays dual roles in both cartilage development and homeostasisGenes Dev. [score:1]
However, their results indicated that miR-140 is dramatically increased in the breast cancer samples [23]. [score:1]
HCT116 and R KO cells (3 × 10 [5] per well) were plated in six-well plates and then transfected with 100 nM of either miR-140 mimic or negative miRNA (Invitrogen) after 24 h with oligofectamine (Invitrogen) according to the manufacturer’s protocols, respectively. [score:1]
The correlation between miR-140 and ADAMTS5 or IGFBP5 expression was calculated using Spearman’s correlation coefficient. [score:1]
miR-140 might be a potential therapeutic candidate for the treatment of CRC. [score:1]
So far we have assessed the significance of miR-140 in the CRC migration and invasion using a gain-in approach. [score:1]
Some contradictions still exist concerning the role of miR-140 in tumor progression and metastasis, and the underlying mechanism is uncertain. [score:1]
The gene encoding microRNA-140-5p (miR-140) is located in chromosome 16. [score:1]
Song B Wang Y Xi Y Kudo K Bruheim S Botchkina GI Gavin E Wan Y Formentini A Kornmann M Fodstad O Ju J Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cellsOncogene. [score:1]
b HCT116 and R KO cells were transfected with miR-140 mimic using oligofectamine. [score:1]
Zhang R Ma J Yao J Molecular mechanisms of the cartilage-specific microRNA-140 in osteoarthritisInflamm Res. [score:1]
Malzkorn et al. [22] reported that miR-140 is one of the increased microRNA candidates in glioma progression from grade II to grade IV. [score:1]
The qRT-PCR analysis of miR-140 was performed in 60 paired human CRC and the matched adjacent noncancerous tissues. [score:1]
a The mRNAs of ADAMTS5 and IGFBP5 contain putative binding sites of miR-140. [score:1]
The successful transfection of miR-140 was verified by qRT-PCR (Fig.   2b). [score:1]
The cell migratory capacity as assessed by transwell migratory assay (without matrigel) showed that miR-140 overexpression significantly decreased migration of the HCT116 cells through the chamber compared with the negative controls (55.2 ± 7.5 vs. [score:1]
Similarly, the cell invasion impact caused by endogenous miR-140 was reversed by knock down assay (Fig.   3f). [score:1]
However, some contradictions still exist concerning the role of miR-140 in tumor progression. [score:1]
[1 to 20 of 99 sentences]
4
[+] score: 317
On the other hand, while RB depletion in MCF-7 cells downregulated hsa-miR-140 expression, overexpression of a constitutively active form RB (RB7LP) [25] significantly upregulated hsa-miR-140 expression (Figure 6G and 6H). [score:13]
In addition, we demonstrated that mmu-miR-140 downregulation induced by Rb depletion was antagonized by RB overexpression (Figure 2E), suggesting that Rb upregulates mmu-miR-140 expression. [score:11]
N = 3. To determine whether the Il-6 mRNA translation is directly suppressed by mmu-mir-140, we constructed luciferase reporter vectors carrying either a wild-type mouse Il-6-3′UTR (mIl-6-3′ UTR-WT) or a mutated target sequence (mIl-6-3′ UTR-Mut) (Figure 5C). [score:8]
N = 3. To determine whether the Il-6 mRNA translation is directly suppressed by mmu-mir-140, we constructed luciferase reporter vectors carrying either a wild-type mouse Il-6-3′UTR (mIl-6-3′ UTR-WT) or a mutated target sequence (mIl-6-3′ UTR-Mut) (Figure 5C). [score:8]
These results indicate that RB upregulates hsa-miR-140 expression, and that the hsa-mir-140-IL6 axis mediates RB function to suppress the self-renewal of human breast cancer cells. [score:8]
Rb depletion indeed upregulated IL-6 expression, which was antagonized by overexpression of mir-140. [score:8]
Inflammatory cytokines, including IL-1β and TNF-α, downregulate mir-140 expression leading to the development of osteoarthritis, most likely due to accelerated inflammation and/or ADAMTS5 activation [44]. [score:7]
Therefore, this study proposes that Rb downregulates IL-6 through upregulation of mir-140. [score:7]
These data implicate that mmu-mir-140 suppresses IL-6 translation by binding to 3′UTR of IL-6 mRNA, therefore may mediate Rb function to suppress tumor progression. [score:7]
These results indicated that both forms of mmu-mir-140 are downregulated by Rb depletion in primary cells; this downregulation was more robust in Rb -depleted secondary cells (Figure 2D). [score:7]
Rb depletion downregulates mir-140 expression. [score:6]
From that subset genes, genes with decreased expression in mir-140 -overexpressed and RB -depleted cells compared with scramble miRNA -overexpressed and Rb -depleted cells were identified, 412 genes total. [score:6]
We observed that the upregulation of IL-6 abundance following RB-depletion in MCF-7 cells was significantly antagonized by hsa-mir-140 overexpression (Figure 6B and 6C); this finding was confirmed by ELISA technique (Figure 6D). [score:6]
To this end, we surveyed genes potentially targeted by mmu-mir-140 among genes that were upregulated by Rb depletion. [score:6]
miRNA expression profiling identifies mmu-miR-140 downregulation in conjunction with this Rb-inactivated undifferentiated state. [score:6]
Figure 2Rb depletion downregulates mir-140 expression(A) Principal components analysis of normalized array data for 252 microRNAs. [score:6]
hsa- mir- 140 suppressed IL-6 upregulation following RB depletion in human breast cancer cellsTo examine whether the hsa-mir-140-IL-6 axis are involved in malignant phenotype induced by RB inactivation in human cancers, we employed MCF-7, a luminal-type breast cancer cell line. [score:6]
Indeed, mmu-mir-140 overexpression significantly antagonized upregulation of Il-6 abundance induced by Rb depletion (Figure 5B). [score:6]
mmu-mir-140 mediates Rb function to control Il-6 expressionWe then focused on Il-6 because it was the most upregulated gene following Rb depletion (Table 1). [score:6]
On the other hand, mmu-mir-140 depletion in Rb intact sarcoma cells was not sufficient to induce robust Il-6 upregulation or increased sphere forming activity (data not shown), suggesting that mmu-mir-140 mediates Rb function to suppress Il-6 and sphere formation in a limited degree. [score:6]
A limitation of this study is that we did not determine how RB upregulates miR-140 expression. [score:6]
The degree of growth suppression was modest; however, mmu-mir-140 overexpression significantly antagonized sphere formation induced by Rb depletion (Figure 3C). [score:5]
hsa-mir-140 suppresses IL-6 expression induced by RB depletion in human breast cancer cells. [score:5]
The gene set induced by Rb depletion in a mir-140 -dependent manner (induced by Rb depletion and suppressed by mir-140 overexpression) was enriched by genes encoding soluble factors mediating immune responses and growth stimuli (Figure 4A, Supplementary Tables 1 and 2), such as Il-6, Il-11, Hgf, Vegfa, Wnt5a, Fgf10 and Serping1 (Figure 4B). [score:5]
Figure 6 hsa-mir-140 suppresses IL-6 expression induced by RB depletion in human breast cancer cells(A) The sequence of the human Il-6 3′UTR and the seed sequence of hsa-mir-140 (underlined) are indicated. [score:5]
Moreover, the addition of recombinant human IL-6 antagonized the inhibition of spherogenesis caused by hsa-mir-140 overexpression in a concentration -dependent manner (Figure 6F). [score:5]
Moreover, addition of recombinant mouse Il-6 significantly blocked the inhibition of spherogenesis caused by mmu-mir-140 overexpression in a concentration -dependent manner (Figure 5E). [score:5]
We found that hsa-mir-140 overexpression significantly suppressed the activity of hIL-6-3′UTR-WT but not hIL-6-3′UTR-Mut (Figure 6I). [score:5]
The mir-140 has been implicated in the suppression of hepatocellular carcinoma, non-small cell lung cancer, colon cancer, breast cancer and ovarian cancer through the inhibition of growth factor signaling [16– 20]. [score:5]
In addition, we performed transcriptome and gene ontology (GO)-enrichment analysis in Rb -depleted and/or mmu-mir-140 -overexpressed soft tissue sarcoma cells by cap analysis gene expression (CAGE). [score:5]
Moreover, reportedly mir-140 expression is implicated in inflammatory disease. [score:5]
mmu-mir-140 antagonizes malignant features induced by Rb depletionSince hsa-mir-140, the human orthologue of mmu-mir-140, has been implicated in tumor suppression [16– 20], we investigated whether mmu-mir-140 mediates Rb function to suppress tumor development in the soft tissue sarcoma mo del. [score:4]
N = 3. Since hsa-mir-140, the human orthologue of mmu-mir-140, has been implicated in tumor suppression [16– 20], we investigated whether mmu-mir-140 mediates Rb function to suppress tumor development in the soft tissue sarcoma mo del. [score:4]
Since both RB and hsa-mir-140 are frequently downregulated in basal-like breast cancer cells [20, 23], which typically show elevated cytokine secretion [24], we focused on human breast cancers. [score:4]
This unveiled a relationship between RB and miR-140; depletion of RB downregulates miR-140. [score:4]
These findings indicate the possibility that mmu-mir-140 mediates the function of Rb to suppress tumor development. [score:4]
Our findings coincide with the recent finding that hsa-mir-140 downregulation promotes cancer stem cell formation in breast cancer cells [20]. [score:4]
Among these six miRNAs, mmu-miR-140 and -337 appeared to be downregulated by Rb deletion in both 2D-cultured and sphere-derived cells. [score:4]
We further identified IL-6 gene as a possible direct target of mir-140. [score:4]
In addition, Il-6 has a mir-140 target sequence in the 3′UTR of both the human and mouse gene. [score:3]
We transduced a lentiviral vector expressing mmu-mir-140 (a precursor of mmu-miR-140 and mmu-miR-140*) or scrambled sequence into control or Rb -depleted cells. [score:3]
Among secreted protein genes, the 3′UTR of VEGF gene can be targeted by hsa-miR-140 [21], and reportedly VEGF gene is induced by RB inactivation [39]. [score:3]
Moreover, hsa-mir-140 has been implicated in the suppression of a variety of human cancers, including breast cancer [16– 20]. [score:3]
In addition, mmu-mir-140 overexpression antagonized in vivo tumorigenicity enhanced by Rb depletion (Figure 3D). [score:3]
We focused on mir-140 in particular because of the significant expression change and conservation between human and mouse. [score:3]
We searched for genes those predicted to be targeted by mmu-mir-140 at microRNA. [score:3]
N = 5. Identification of genes regulated by Rb in a mmu- mir- 140 -dependent mannerTo further explore the possibility that mir-140 may mediate the tumor-suppressive function of RB, we investigated genes regulated by Rb in a mir-140 -dependent manner. [score:3]
Identification of the mir-140-target gene that contributes to Rb depletion -induced malignant phenotype. [score:3]
Figure 5 mmu-mir-140 mediates Rb function to control Il-6 expression(A) RT-qPCR of Il-6 in p53 -null soft tissue sarcoma cells transduced with the indicated shRNA and retroviral vectors. [score:3]
We validated the expression of mmu-miR- 140-5p (miR-140) and mmu-miR-140-3p (miR-140*) in the three cell types by reverse transcription-quantitative PCR (RT-qPCR) (Figure 2D and Supplementary Figure 2A). [score:3]
The 3′UTR regions in these genes appeared to have highly possible mir-140 target sequence (Figure 4C). [score:3]
N = 3. (I) h IL-6-3′UTR WT or h IL-6-3′UTR Mut was transduced into MCF-7 cells together with the hsa-mir-140 expression vector or control (scramble). [score:3]
We found that mmu-mir-140 overexpression did not induce apoptosis but attenuated the cell growth of both control and Rb depleted cells in 2D culture (Figure 3B and Supplementary Figure 3A and 3B). [score:3]
mmu-mir-140 mediates Rb function to control Il-6 expression. [score:3]
We found that mmu-mir-140 overexpression significantly repressed the activity of mIl-6-3′ UTR-WT but not mIl-6-3′ UTR-Mut (Figure 5D). [score:3]
As mentioned above, the human IL-6 gene has a hsa-mir-140 target sequence in its 3′UTR (Figure 6A). [score:3]
We verified mmu-miR-140 expression in transduced cells by RT-qPCR (Figure 3A). [score:3]
We identified genes that had less than 0.5 mirSVR score to mmu-mir-140 as candidate genes regulated by Rb in a mir-140 dependent manner (Table 1). [score:2]
N = 5. To further explore the possibility that mir-140 may mediate the tumor-suppressive function of RB, we investigated genes regulated by Rb in a mir-140 -dependent manner. [score:2]
We however point out that miR-140 is not solely a mechanism that links RB to IL-6, since as compared to the mild effect of RB depletion on hsa-miR-140 expression in MCF-7 cells, IL-6 induction was more robust (Figure 6H and 6B). [score:2]
Both mmu-mir-140 and hsa-mir-140 are encoded in an intronic region of WWP2 gene encoding an E3 ubiquitin ligase. [score:1]
These genes exhibited high mirSVR scores to miR-140 and/or miR-140*, and were sorted according to the p value of their rpkm values. [score:1]
mmu-mir-140 antagonizes the malignant features induced by Rb depletion. [score:1]
Determination of mir-140 -dependent Rb inactivation signature. [score:1]
N = 3. (E) RT-qPCR of miR-140 in p53 -null soft tissue sarcoma cells transduced with the indicated vector. [score:1]
Combined with the information indicating the pivotal role of RB in the malignant progression of breast cancer [26– 28], we anticipated a functional interaction between RB and hsa-mir-140. [score:1]
Figure 4Identification of genes induced by Rb depletion in a mir-140 -dependent manner(A) The ontology of the top 3 gene sets influenced by Rb depletion possibly in an mir-140 -dependent manner was determined by GO Biological Process provided by DAVID. [score:1]
We also mutated complementary seed sequences in the miR-140 -binding region (See Figure 4B and Supplementary Figure 4A), and generated the reporter construct Il-6-3′ UTR Mut. [score:1]
Figure 3 mmu-mir-140 antagonizes the malignant features induced by Rb depletion(A) RT-qPCR of mmu-miR-140 in p53 -null sarcoma cells transduced with the indicated vector. [score:1]
In addition, mmu-miR-140 sequence was conserved between mouse and human (Figure 2C). [score:1]
Of these two miRNAs, mmu-miR-140 exhibited more robust fold change. [score:1]
Murine microRNA precursor constructs for mmu-mir-140 (MMIR-140-PA-1) and mouse precursor scramble negative control (MMIR-000-PA-1) were purchased from System Biosciences (Mountain View, USA). [score:1]
mmu-mir-140 antagonizes malignant features induced by Rb depletion. [score:1]
Because RB is prevalently inactivated by various oncogenic signals during the malignant progression of many types of cancers, mir-140 can potentially serve as a therapeutic tool for disrupting linkages of oncogenic signals to inflammatory responses, cell proliferation, or pro-angiogenic responses. [score:1]
N = 3. To examine whether the hsa-mir-140-IL-6 axis are involved in malignant phenotype induced by RB inactivation in human cancers, we employed MCF-7, a luminal-type breast cancer cell line. [score:1]
N = 3. (C) The sequence of the mouse Il-6 3′UTR containing seed sequence of mmu-mir-140 (underlined). [score:1]
This work proposes that the RB-miR-140-IL-6 axis may play a critical role in cancer stem cells. [score:1]
N = 3. (H) RT-qPCR of hsa-miR-140 in MCF-7 cells transduced with the indicated vector. [score:1]
Identification of genes induced by Rb depletion in a mir-140 -dependent manner. [score:1]
In addition, hsa-mir-140 antagonized enhancement of sphere-forming activity induced by RB depletion (Figure 6E). [score:1]
NIH3T3 cells were transfected with 0.5 μg reporter construct, either 3.0 μg mmu-miR-140 construct or 3.0 μg scramble control construct, and 0.25 μg β-galactosidase using 100 μl Opti-MEM (Life Technologies) and 11.25 μl FuGENE6 (Promega Corporation, Cat. [score:1]
MCF-7 cells were transfected with 0.05 μg reporter construct and either 0.3 μg hsa-miR-140 construct or 0.3 μg scramble control construct using 10 μl Opti-MEM (Life Technologies, Cat. [score:1]
N = 5. (A) RT-qPCR of mmu-miR-140 in p53 -null sarcoma cells transduced with the indicated vector. [score:1]
In addition to Il-6, the genes induced by Rb depletion possibly in a mir-140 -dependent manner included those encoding various secreted proteins such as proteases, growth factors, cytokines, and chemokines (Table 1). [score:1]
For these reasons, our subsequent studies focused on mmu-miR-140. [score:1]
[1 to 20 of 85 sentences]
5
[+] score: 295
Other miRNAs from this paper: hsa-mir-22, hsa-mir-27a, hsa-mir-27b, hsa-mir-145, hsa-mir-146a
However, the expression of miR-140 was upregulated in a concentration -dependent manner (Fig.   1b) miR-140 expression in primary chondrocytes was rapidly induced (within 4 hours) by E2 treatment, and expression levels gradually increased over a 12-hour period (Fig.   1c). [score:10]
Cont control, E2 17-β-estradiol, GAPDH glyceraldehyde 3-phosphate dehydrogenase, IL-1β interleukin-1 beta, MMP-13 metalloproteinase 13 Our data demonstrated that E2 can suppress MMP-13 expression and upregulate miR-140 expression. [score:10]
Thus, miR-140 expression was found to be necessary for the significant inhibitory effect of E2 on IL-1β -induced MMP-13 expression Fig. 4E2 acts via the ER/miR-140 pathway to suppress IL-1β -mediated catabolic responses in chondrocytes. [score:9]
miR-140 levels were upregulated or downregulated by transfecting cells with a miRNA mimic and inhibitor, respectively, prior to treatment with IL-1β. [score:9]
Furthermore, IL-1β -induced activation of signal transduction pathways associated with the expression of MMP-13 downregulated the expression of miR-140. [score:8]
Interestingly, miR-140 overexpression by transfection with the miR-140 mimic significantly reduced the expression of MMP-13 in E2 -treated IL-1β-stimulated human chondrocytes (Fig.   4c and d) Thus, our results suggest that miR-140 is a crucial regulator of E2 -mediated cartilage homeostasis, where miR-140 enables E2 to suppress IL-1β -induced MMP-13 production. [score:8]
miR-140 is also a negative regulator of MMP-13, and miR-140 expression is downregulated in OA [29– 32]. [score:7]
E2 17-β-estradiol, GAPDH glyceraldehyde 3-phosphate dehydrogenase, IL-1β interleukin-1 beta, MMP-13 metalloproteinase 13 In order to determine whether the upregulation of miR-140 is transcriptionally dependent on E2, we analyzed the promoter region of miR-140 and found two putative ERE binding sites for ER in the region upstream of miR-140, suggesting that ER may modulate miR-140 expression directly (Fig.   5a). [score:7]
Knockdown of miR-140 expression abolished the inhibitory effect of estrogen on MMP-13. [score:6]
We also showed that E2 stimulation upregulates the expression levels of miR-140 in chondrocytes. [score:6]
ER induction upregulates miR-140 expression. [score:6]
To examine the role of miR-140 in the downregulation of MMP-13 by E2 and to determine whether modulation of miR-140 can control the pathogenesis of OA in vitro, chondrocytes were transfected either with a miR-140 mimic or a miR-140 inhibitor. [score:6]
However, this downregulation of miR-140 expression was blocked by E2 (Fig.   3b). [score:6]
miR-140 expression was upregulated after estrogen treatment. [score:6]
d Western blot of MMP-13 expression in normal chondrocytes transfected with miR-140 inhibitor or miR-140 mimic pretreated and untreated with IL-1β (5 ng/ml) for 4 hr, then treated with10 nM E2 for 24 hr. [score:5]
Taken together, these data strongly indicate that E2 regulates MMP-13 gene expression in human chondrocytes via the miR-140 regulatory pathway. [score:5]
Moreover, miR-140 inhibits MMP-13 expression in articular chondrocytes [37]. [score:5]
c Kinetics of expression of miR-140 expression treated with E2 (10 nM) for 4, 8, 12 and 24 hr in OA chondrocytes from female patients. [score:5]
Cartilage-specific miR-140 was one of the first miRNAs found to be abundantly expressed in chondrocytes and has been shown to critically regulate cartilage development and homeostasis. [score:5]
For example, the expression of miR-140 is directly regulated by Sox9 [38, 39]. [score:5]
Treatment with miR-140 dramatically increased the inhibitory effect of E2 on MMP-13 in IL-1β -treated chondrocytes, whereas treatment with miR-140 inhibitor dramatically enhanced MMP-13 levels with IL-1β treatment. [score:5]
For example, miR-140 directly targets the gene that encodes a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS-5), an aggrecanase that cleaves aggrecan in cartilage. [score:4]
ER estrogen receptor, IL-1β interleukin-1 beta, MMP-13 metalloproteinase 13 Our data demonstrated that ER regulated the expression of miR-140 in both normal and OA chondrocytes. [score:4]
Yang J Qin S Yi C Ma G Zhu H Zhou W MiR-140 is co-expressed with Wwp2-C transcript and activated by Sox9 to target Sp1 in maintaining the chondrocyte proliferationFEBS Lett. [score:4]
Thus, ER/miR-140 may play a role in regulating the expression of MMP-13 in human chondrocytes. [score:4]
b Relative expression of miR-140 in normal chondrocytes pretreated with IL-1β (5 ng/ml) for 4 hr, then treated with 10 nM E2 for 24 hr. [score:3]
b Relative expression of miR-140 in female OA chondrocytes stimulate with different concentration of E2 for 12 hr. [score:3]
In addition, the estrogen/ER/miR-140 pathway showed an inhibitory effect on IL-1β -induced cartilage matrix degradation. [score:3]
Gene expression levels of miR-140, MMP-13, and ADAMTS-5 were detected by quantitative real-time PCR (qRT-PCR). [score:3]
These findings provide new insight into the mechanism of menopausal arthritis and indicate that the ER/miR-140 signaling pathway may be a potential target for therapeutic interventions for menopausal arthritis. [score:3]
b Relative MMP-13 mRNA in normal chondrocytes transfected with miR-140 inhibitor then stimulated with IL-1β (5 ng/ml) for 4 hr, then treated with 10 nM E2 for 24 hr. [score:3]
Twenty-four hours after plating, 100 nmol of has-miR-140-5p mimic or 100 nM scrambled 22 nt nucleotides (miR-Scr, with no homology to mammal genome) or 150 nM inhibitors (designed and synthesized by RiboBio, Guangzhou, China) were transfected to the cells with Lipofectamine RNAiMAX (Invitrogen) following the manufacturer’s protocol. [score:3]
Pre-transfection of IL-1β -induced chondrocytes with the miR-140 inhibitor abolished the E2 -mediated reduction of endogenous levels of MMP-13 transcripts and proteins (Fig.   4b and d). [score:3]
Fig. 6Schematic diagram to show E2 modulation of miR-140 in IL-1β induced MMP-13 expression. [score:3]
IL-1β -induced expression of MMP-13 and miR-140 is blocked by E2. [score:3]
Fig. 1E2 induced miR-140 expression in time and concentration dependent. [score:3]
from this study suggest that ER/miR-140 may serve as a potential therapeutic target for OA treatment. [score:3]
LSox5 and Sox6 can also control miR-140 expression through a response element in the miR-140 promoter [40]. [score:3]
Chondrocytes (2.5 × 10 [4] cells per well in a 24-well plate) were planted and transfected with miR-140 inhibitor, miR-140 mimic, and their negative controls (miR-Scr) up to 24 hr. [score:3]
Our results demonstrate that miR-140 acts as an intermediary transcriptional factor to suppress MMP-13 and IL-1β responses in human chondrocytes. [score:3]
a Transfection efficiency of miR-140 inhibitor and miR-140 mimic in chondrocytes. [score:3]
We hypothesized that the inhibiting effect of E2 on MMP-13 may be mediated by miR-140. [score:3]
The transcription factors involved in miR-140 expression in OA pathogenesis are also unknown. [score:3]
Therefore, ligand -dependent activation of ER increased ERE -mediated miR-140 promoter activity, resulting in MMP-13 suppression. [score:3]
Fig. 3Effect of E2 on MMP-13 and miR-140 expression in IL-1β-stimulated chondrocytes. [score:3]
E2 17-β-estradiol, ERα estrogen receptor alpha Previous studies reported that miR-140 expression was lower in OA cartilage than in normal cartilage [31]. [score:3]
c Relative expression of MMP-13 in normal chondrocytes transfected with miR-140 mimic and pretreated with IL-1β (5 ng/ml) for 4 hr, then treated with 10 nM E2 for 24 hr. [score:3]
Thus, miR-140 could be regulated by binding ER directly. [score:3]
Subsequently, the expression of miR-140 in IL-1β-stimulated human chondrocytes was quantified. [score:3]
E2 modulates MMP-13 transcript expression via miR-140 in human chondrocytes. [score:3]
These findings suggest that miR-140 mediates the inhibitory effect of E2 on MMP-13. [score:3]
E2 promotes miR-140 expression by activating ERE. [score:3]
d E2 induction of miR-140 expression was significantly repressed by estrogen receptor alpha RNAi. [score:3]
As expected, miR-140 expression was significantly decreased in chondrocytes following IL-1β stimulation. [score:3]
This study suggests that estrogen acts via ER and miR-140 to inhibit the catabolic activity of proteases within the chondrocyte extracellular matrix. [score:3]
Thus, we speculate that the E2-stimulated increase in miR-140 levels exerts an inhibitory effect on MMP-13. [score:3]
Yamashita S Miyaki S Kato Y Yokoyama S Sato T Barrionuevo F L-Sox5 and Sox6 proteins enhance chondrogenic miR-140 microRNA expression by strengthening dimeric Sox9 activityJ Biol Chem. [score:3]
E2 induction of miR-140 expression was significantly repressed by estrogen receptor alpha RNAi (Fig.   1d). [score:3]
Estradiol stimulated miR-140 -driven luciferase reporter activity, which suggests that ER can directly activate miR-140 transcription. [score:2]
Thus, this study provides novel insights into how to “fine-tune” ER -dependent signaling for the control of menopausal OA and may facilitate the development of therapeutic approaches based on the modulation of the ER/miR-140 pathway. [score:2]
E2 regulates miR-140 and thereby alters MMP-13 activity (Fig.   6). [score:2]
Thus, these data present new evidence that miR-140 is an early ER-regulated gene. [score:2]
Tardif G Hum D Pelletier JP Duval N Martel-Pelletier J Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytesBMC Musculoskelet Disord. [score:2]
Our findings also prompted us to investigate whether E2 upregulates miR-140 could attenuates menopausal OA in an OVX mouse mo del. [score:2]
This study aimed to determine the role of miR-140 in the estrogen -dependent regulation of MMP-13 in human chondrocytes. [score:2]
However, the mechanism that underlies miR-140 -mediated regulation upstream of its effects on ADAMTS-5 and MMP-13 is currently unclear. [score:2]
Thus, miR-140 may be a regulator of cartilage homeostasis in OA. [score:2]
We propose that ER transcriptional activity regulates miR-140 after estradiol -mediated ER activation. [score:2]
To further investigate the involvement of miR-140 in the regulation of MMP-13 by E2 in human articular chondrocytes, normal chondrocytes were treated with a miR-140 mimic or a miR-140 inhibitor in the presence of IL-1β, and MMP-13 transcript levels were quantified. [score:2]
This indicated that the 495 bp region upstream from miR-140 is required for its regulation by E2. [score:2]
-pmiR-140) and two miR-140 promoter mutants (mut −336/-321 and mut −306/-318), 12 hr after transfection, the cells were serum starved for 12 hr followed by 4-hr treatment with E2 (10 nM). [score:1]
Previous studies reported that the proximal region upstream of the pri-miR-140 gene can bind chondrocyte-specific transcriptional factors in vivo. [score:1]
b Luciferase activity in SW1353 cells transfected with miR-140 promoter wide-type (pGL3. [score:1]
Miyaki S Sato T Inoue A Otsuki S Ito Y Yokoyama S MicroRNA-140 plays dual roles in both cartilage development and homeostasisGenes Dev. [score:1]
In summary, the present study demonstrates that the ER/miR-140/MMP-13 pathway is responsible for cartilage degradation in human OA chondrocytes. [score:1]
To confirm the activation effect of miR-140 promoter activity, SW1353 human chondrosarcoma cells were transiently transfected using Lipofectamine 2000 (Invitrogen) according to the manufacturer’s instructions. [score:1]
Altogether, these results demonstrated that the E2 ligand activates the transcription factor ER, which then binds to specific ERE sequences in the promoter region of miR-140 and positively enhances its transcription. [score:1]
The miR-140 promoter sequence contains a classical estrogen response element (ERE) with the consensus sequence 5′-GGTCAnnnTGACC-3′ [41, 42]. [score:1]
Our study demonstrated that miR-140 promoter activity was modulated by estrogen in chondrocytes. [score:1]
Nakamura Y He X Kato H Wakitani S Kobayashi T Watanabe S Sox9 is upstream of microRNA-140 in cartilageAppl Biochem Biotechnol. [score:1]
The transfection efficiency was quantified by miR-140-5p qRT-PCR. [score:1]
a −495 proximal region sequence upstream of the miR-140 star sequence contains two classical estrogen response elements with the consensus sequence 5′-GGTCAnnnTGACC-3′. [score:1]
Liang ZJ Zhuang H Wang GX Li Z Zhang HT Yu TQ MiRNA-140 is a negative feedback regulator of MMP-13 in IL-1β-stimulated human articular chondrocyte C28/I2 cellsInflamm Res. [score:1]
Estrogen-bound estrogen receptor alpha (ERα) was shown to initiate the transcription of miR-140 by associating with its ER response element (ERE) element. [score:1]
Since miR22, miR27b, miR-145, miR-146a, and miR-140 have been linked to the pathophysiology of OA [36], we first evaluated the expression of these miRNA following E2 stimulation. [score:1]
In menopausal OA conditions, low estrogen levels reduce the induction of ER/miR-140, resulting in increased MMP-13 activity. [score:1]
Fig. 5E2 stimulation activates human miR-140 promoter activity and is mediated by the −336/-321- and −306/-318- bp sequences. [score:1]
[1 to 20 of 87 sentences]
6
[+] score: 294
The insulin-like growth factor-1 receptor (IGF1R) oncogene, which is frequently overexpressed in many malignancies and functions as an important regulator of cell proliferation, survival, and metastasis [26– 29], was identified as a critical downstream target of miR-140, and this conclusion is supported by the following evidence: (A) complementary sequence of miR-140 is identified in the 3’ UTR of IGF1R mRNA; (B) overexpression of miR-140 significantly reduced IGF1R levels in NSCLC cells, whereas knockdown of miR-140 enhancedIGF1R expression; (C) miR-140 overexpression reduced the activity of a luciferase reporter containing the wild-type 3’ UTR of IGF1R mRNA; (D) the inhibitory effects of miR-140 on NSCLC cell proliferation, apoptosis, and invasion were reversed by overexpression of IGF1R; (F) IGF1R was upregulated in NSCLC tissues and inversely correlated with the expression levels of miR-140. [score:22]
Taken together, these results suggest that miR-140 down-regulates IGF1R expression by directly targeting its 3’ UTR. [score:9]
Furthermore, we identified IGF1R as a target gene of miR-140 and confirmed that miR-140 exerts its effect on the inhibition of tumor growth and metastasis by downregulating IGF1R. [score:8]
Overexpression of miR-140 inhibits tumor growth and metastasis of NSCLC through directly targeting IGF1R. [score:8]
Furthermore, qRT-PCR and analysis demonstrated that overexpression of miR-140 substantially decreased the expression of IGF1R in A549 and H157 cells, and that knockdown of miR-140 increased IGF1R expression in H520 cells (Figure 5C and D). [score:8]
Our data suggest that the frequently downregulated miR-140 leads to the increased expression of IGF1R and in turn contributes to the development and progression of NSCLC. [score:7]
More recently, Yang and colleagues reported that miR-140-5p is significantly decreased in HCC tissues and cell lines, and its overexpression suppresses tumor growth and metastasis by targeting transforming growth factor β receptor 1 and fibroblast growth factor 9 [20]. [score:7]
miR-140 downregulates IGF1R by directly targeting its 3’ UTR. [score:7]
Overexpression of miR-140 could effectively inhibit NSCLC cell proliferation, induce cell cycle arrest, enhance apoptosis, and suppress tumor growth in nude mice. [score:7]
Together, these data strongly suggest that miR-140 inhibits NSCLC growth and metastasis through downregulating IGF1R. [score:6]
To further examine whether miR-140 exerts its tumor suppressor function through downregulation of IGF1R, we performed gain-of-function and loss-of-function analyses. [score:6]
Taken together, these results indicate that miR-140 overexpression can suppress the tumorigenesis and metastasis of NSCLC cells in vivo. [score:5]
Song et al. showed that overexpression of miR-140 inhibited cell proliferation in both osteosarcoma and colon cancer cell lines [19]. [score:5]
We found that Overexpression of miR-140 inhibited tumor growth, invasion, and metastasis of NSCLC cells. [score:5]
To elucidate the molecular mechanisms by which miR-140 executes its function, we searched for potential targets of miR-140 using different computational methods, such as TargetScan and miRanda. [score:5]
The inhibitory effect of miR-140 on cell invasion was also antagonized by IGF1R overexpression (Figure 6E). [score:5]
To elucidate the underlying mechanisms involved in the miR-140 -induced inhibition on NSCLC growth and metastasis, we used different prediction algorithms to predict gene targets for miR-140. [score:5]
Overexpression of miR-140 inhibits cell proliferation, induces cell apoptosis and cell cycle arrest in G1 phase in both A549 and H157 cells. [score:5]
As shown in Figure 6B, C and D, overexpression of IGF1R significantly rescued miR-140 -induced cell growth inhibition, cell-cycle arrest and apoptosis. [score:5]
IGF1R was identified as one candidate target of miR-140, because the complementary sequence of miR-140 was identified in its 3’ UTR by TargetScan analysis (Figure 5A). [score:5]
To validate whether IGF1R is the direct downstream target of miR-140, a fragment of IGF1R 3’ UTR containing the putative miR-140 binding site was cloned into a luciferase reporter vector. [score:4]
Taken together, these results suggest that the downregulation of miR-140 may play important roles in NSCLC carcinogenesis and progression. [score:4]
miR-140 is downregulated in NSCLC tissues and cell lines. [score:4]
To better understand the role of miR-140 in the development of NSCLC, we first constructed a lentiviral vector expressing miR-140 and established stable cell lines, denoted as A549-miR-140 and H157-miR-140 after lentivirus infection. [score:4]
As shown in Figure 2B, overexpression of miR-140 significantly suppressed cell proliferation of A549 and H157 cells compared with their corresponding controls. [score:4]
In conclusion, the present study showed that miR-140 is significantly downregulated in NSCLC tissues and cell lines. [score:4]
The statistical analysis revealed that the downregulation of miR-140 was significantly correlated with tumor stage and metastasis while no significant correlation was observed in other parameters (Table 1). [score:4]
These findings suggest that miR-140 functions as a tumor-suppressor role in these cancers; however, to our knowledge, its roles and the potential mechanisms in NSCLC remains unclear. [score:3]
Taken together, these data demonstrate that IGF1R is a functional target of miR-140. [score:3]
These results suggest that miR-140 might be a novel tumor-suppressor miRNA in NSCLC. [score:3]
Furthermore, the correlation between miR-140 expression levels and clinicopathologic parameters was analyzed. [score:3]
Taken together, these results suggest that miR-140 can suppress NSCLC cell migration and invasion in vitro. [score:3]
These results were similar to the effects of miR-140 overexpression. [score:3]
IGF1R is involved in miR-140 -induced suppression of NSCLC cell growth and invasion. [score:3]
In addition, a statistically significant inverse correlation was observed by Spearman’s correlation analysis between expression levels of miR-140 and IGF1R mRNA (Figure 5B). [score:3]
miR-140 inhibits tumor growth and metastasis in NSCLC cells in nude mice. [score:3]
miR-140 suppresses tumor growth and metastasis of NSCLC in nude mice. [score:3]
0073604.g002 Figure 2(A) A549 and H157 cells were infected with miR-140 or miR-control lentivirus, and the expression of miR-140 was analyzed by qRT-PCR. [score:3]
Expression of miR-140 is decreased in NSCLC tissues and cell lines. [score:3]
Furthermore, we examined the effect of miR-140 overexpression on NSCLC metastasis in vivo. [score:3]
Successful overexpression of mature miR-140 in these cells was confirmed by qRT-PCR (Figure 2A). [score:3]
To study the expression and significance of miR-140 in NSCLC carcinogenesis, we measured the expression of miR-140 in 30 pairs of NSCLC tissues and their matched normal lung tissues using quantitative reverse transcriptase PCR (qRT-PCR). [score:3]
In addition, the expression of miR-140 in five NSCLC cell lines was determined. [score:3]
Site-directed mutagenesis of the miR-140 seed sequence in the IGF1R 3’-UTR (Mut) was performed using the QuikChange™ Site-Directed Mutagenesis Kit (Stratagene, La Jolla, CA, USA). [score:3]
miR-140 inhibits NSCLC cell proliferation in vitro. [score:3]
Using the wound healing assay, we found that overexpression of miR-140 dramatically suppressed tumor cell mobility in A549 and H157 cells compared with their corresponding controls (Figure 3A). [score:3]
In the present study, we focused on miR-140, which has been indicated to be a possible tumor suppressor in human malignances. [score:3]
In this study, we showed that miR-140 expression was significantly decreased in NSCLC tissues and cell lines. [score:3]
The relationship between miR-140 expression and clinicopathologic parameters in NSCLC. [score:3]
In consistent with these results, miR-140 overexpression triggered an accumulation of cells at G1 phase, and decreased the number of cells at S phase in both cell lines (Figure 2D). [score:3]
The miR-140 inhibitor and negative control were obtained from Genepharma (Shanghai, China). [score:3]
IGF1R is a downstream target of miR-140. [score:3]
Our findings demonstrate a novel role of miR-140 as a tumor suppressor in NSCLC. [score:3]
IGF1R is involved in miR-140 -induced growth and invasion inhibition in A549 cells. [score:3]
Luciferase reporter assays showed that up-regulation of miR-140 significantly decreased the relative luciferase activity of IGF1R-3’UTR in A549 and H157 cells, but had no effect on the mutant of IGF1R-3’UTR (Figure 5E). [score:3]
miR-140 suppresses NSCLC cell migration and invasion in vitro. [score:3]
Furthermore, miR-140 overexpression significantly repressed cell motility and invasion in vitro and tumor metastasis in vivo. [score:3]
miR-140 overexpression was also found to induce cell apoptosis in A549 and H157 cells (Figure 2C). [score:3]
Accordingly, knockdown of miR-140 promoted cell proliferation and invasion. [score:2]
Taken together, these results demonstrate that miR-140 is able to regulate NSCLC cell growth. [score:2]
As shown in Figure 1B, the relative expression levels for miR-140 in these NSCLC cells were significantly decreased compared with that of the normal cell line BEAS-2B. [score:2]
For tumor growth assays, A549 cells infected with either the miR-140 -overexpressing lentivirus or the control lentivirus were injected subcutaneously into the right scapulas of nude mice (5-week-old BALB/c-nu/nu, 5 per group, 1.5×10 [6] cells for each mouse). [score:2]
The results illustrated that miR-140 -overexpressing tumors were significantly smaller in size and tumor volume compared to the control tumors (Figure 4A and B). [score:2]
Mutation was generated in the IGF1R 3’ UTR by mutating 3 nt that is recognized by miR-140. [score:2]
The results showed that miR-140 expression was significantly decreased in NSCLC tissues compared with their matched normal tissues (Figure 1A). [score:2]
In contrast, knockdown of miR-140 using anti-miR-140 in H520 cells promoted cell growth, while no significant change in cell cycle and cell apoptosis was detected (Figure S1). [score:2]
miR-140 has attracted much attention because it is involved in the development and progression of various types of cancers, including breast cancer, osteosarcoma, colon cancer and hepatocellular carcinoma [18– 20]. [score:2]
0073604.g006 Figure 6A549 cells were infected with specific si IGF1R, or transfected with IGF1R plasmid lacking 3’ UTR along with miR-140. [score:1]
0073604.g001 Figure 1(A) the expression levels of miR-140 in 30 pairs of NSCLC tissues and their matched normal lung tissues were measured by qRT-PCR. [score:1]
The miR-140 precursor and IGF1R siRNA were purchased from Origene (Rockville, Maryland, USA). [score:1]
We further investigated whether miR-140 could also inhibit cell migration and invasion in NSCLC. [score:1]
The pre-miR-140 sequence and IGF1R siRNA sequence were cloned into pCDH-CMV-MCS-EF1-coGFP constructs (System Biosciences, California, USA). [score:1]
To date, however, the role of miR-140 in NSCLC carcinogenesis and the molecular mechanisms by which miR-140 exerts its functions remain unclear. [score:1]
A549-miR-140 cells and A549-miR-control cells were injected into nude mice by caudal vein injections. [score:1]
In this study, we provide the first evidence for a role of miR-140 in NSCLC tumorigenesis and progression, and partially elucidates the molecular mechanism underlying this effect. [score:1]
In contrast, the wound healing and invasion of H520 cells was increased when endogenous miR-140 was silenced with anti-miR-140 (Figure S1). [score:1]
The correlation between miR-140 and IGF1R expression was evaluated using Spearman’s correlation analysis. [score:1]
Subsequently, A549-miR-140 cells were transfected with IGF1R plasmids lacking 3’ UTR. [score:1]
Figure S1 Konckdown of miR-140 promotes cell proliferation, migration, and invasion of H520 cells. [score:1]
To further determine the effect of miR-140 on NSCLC tumor growth and metastasis in vivo, A549-miR-140 cells and A549-miR-control cells were inoculated subcutaneously into the flank of nude mice and the animals were closely monitored for tumor growth for 5 weeks. [score:1]
A549 cells were infected with specific si IGF1R, or transfected with IGF1R plasmid lacking 3’ UTR along with miR-140. [score:1]
0073604.g005 Figure 5(A) putative binding sequences of miR-140 in the IGF1R 3’ UTR. [score:1]
[1 to 20 of 82 sentences]
7
[+] score: 252
Other miRNAs from this paper: hsa-mir-30a, hsa-mir-196a-1, hsa-mir-196a-2, hsa-mir-196b
To confirm that the inhibitory effect of miR-140-5p on ip3k2 3′-UTR reporter expression was mediated specifically via predicted miR-140-5p target sites located in the ip3k2 3′-UTR, mutations were introduced in the seed sequences of both target sites in the reporter construct (Figure 4A). [score:10]
Overexpression of miR-140-5p up-regulates anticancer drug -induced autophagy in osteosarcoma cellsTo determine the possible contribution of miR-140-5p to autophagy in drug -treated osteosarcoma cells, miR-140-5p expression was manipulated in Saos-2 cells via transfection with miR-140-5p mimics or miRNA control. [score:8]
In the present study, we determined the targeting role of miR-140-5p (miRBase ID: MIMAT0000431) to inositol 1,4,5-trisphosphate kinase 2 (IP3K2), the regulation of miR-140-5p on the IP3K2 -mediated cell autophagy during chemotherapy, and the suppression of miR-140-5p inhibitor in the cell proliferation of osteosarcoma cells. [score:8]
Figure 1 miR-140-5p expression was up-regulated in osteosarcoma cells following treatment with chemotherapeutic drugsqPCR analysis showing the relative miR-140-5p expression to U6 in (A) Saos-2 and (B) MG-63 cells. [score:8]
Mutation of target site partially eliminated the inhibitory effect of miR-140-5p mimics on reporter expression (Figure 4E). [score:8]
In summary, our study shows that miR-140-5p targeted IP3k2 and inhibited the IP3k2 -mediated autophagy in osteosarcoma cells during the chemotherapy, and sensitized the osteosarcoma cells to anticancer drugs by inhibiting cell proliferation. [score:7]
miR-140-5p inhibits IP3k2 expression via predicted 3′-UTR target sites. [score:7]
miR-140-5p inhibits IP3k2 expression via predicted 3′-UTR target sitesTo validate the functionality of the putative miR-140-5p/ ip3k2 3′-UTR interaction, a reporter construct was prepared containing the full-length ip3k2 3′-UTR. [score:7]
Therefore, miR-140-5p mediates its inhibitory effect on ip3k2 3′-UTR reporter expression by interacting with at least one of predicted target sites in the ip3k2 3′-UTR. [score:7]
Figure 3Overexpression of miR-140-5p up-regulated anticancer drug -induced autophagy in osteosarcoma cells(A) LC3 punctas under fluorescence microscopy in Saos-2 cells following 0.1 μg/ml Dox or 10 μM Cis treatment and miR-140-5p mimics or miR-control transfection. [score:6]
The present study has demonstrated that anticancer drug treatment up-regulates miR-140-5p expression in osteosarcoma cells. [score:6]
Overexpression of miR-140-5p up-regulated anticancer drug -induced autophagy in osteosarcoma cells. [score:6]
Next, we tested whether the predicted target of miR-140-5p was down-regulated in response to drug treatment. [score:6]
In conclusion, the present study has demonstrated that anticancer drug treatment up-regulates miR-140-5p expression in osteosarcoma cells. [score:6]
miR-140-5p targets the IP3k2 protein to regulate autophagy during osteosarcoma cell deathOur next goal was to identify targets of miR-140-5p that influence autophagy. [score:6]
Overexpression of miR-140-5p up-regulates anticancer drug -induced autophagy in osteosarcoma cells. [score:6]
The results indicated that treatment with 0.2 μg/ml Dox or 20 μM Cis significantly up-regulated the miR-140-5p expression levels in the two cell lines. [score:6]
miR-140-5p expression was up-regulated in osteosarcoma cells following treatment with chemotherapeutic drugs. [score:6]
Figure 2Inhibition of miR-140-5p ameliorated the anticancer drug -induced cell proliferation decrease in vitro(A and B) Osteosarcoma cells were transfected with miR-140-5p inhibitor or a scrambled control. [score:5]
miR-140-5p inhibited IP3k2 expression in osteosarcoma cells. [score:5]
Taken together, these results suggested that exogenous miR-140-5p likely inhibits IP3k2 expression via mRNA destabilization. [score:5]
Thus, we identified the tumour suppressive role of miR-140-5p inhibitor in osteosarcoma cells in vitro. [score:5]
We used the miRNA binding site prediction programmes Pictar and Targetscan to identify candidate miR-140-5p target genes. [score:5]
Figure 4 miR-140-5p inhibited IP3k2 expression in osteosarcoma cells(A) The binding sites and the corresponding mutated sequences within the ip3k2 3′-UTR for miR-140-5p were presented. [score:5]
Co-transfection of the reporter construct along with miR-140-5p mimics in Saos-2 cells resulted in significantly reduced Renilla activity relative to co-transfection with negative control mimic or transfection of reporter construct alone (53% of negative control mimics) suggesting an inhibitory regulatory interaction between miR-140-5p and the ip3k2 3′-UTR. [score:4]
The increased miR-140-5p expression facilitated tumour cell proliferation via up -regulating autophagy, thus, facilitated the resistance of osteosarcoma cells to Dox or Cis. [score:4]
miR-140-5p targets the IP3k2 protein to regulate autophagy during osteosarcoma cell death. [score:4]
Inhibition of miR-140-5p promotes the anticancer drug -induced cell proliferation decreaseTo determine the possible effect of miR-140-5p on osteosarcoma cell proliferation, the proliferation of Saos-2 or MG-63 cells that had been treated with Dox or Cis and transfected with miR-140-5p inhibitors was determined using a CCK-8 assay. [score:4]
miR-140-5p expression increases in osteosarcoma cells following treatment with chemotherapy agentsThe role of miRNAs in chemotherapy -induced autophagy of cancer cells remains unknown. [score:3]
These results confirm that overexpression of miR-140 contributes to anticancer drug -induced autophagy in osteosarcoma cells. [score:3]
miR-140-5p mimic, miR-140-5p inhibitor and the corresponding control oligonucleotides (purchased from RiboBio) were transfected into cells as described previously [36]. [score:3]
miR-140-5p expression increases in osteosarcoma cells following treatment with chemotherapy agents. [score:3]
miR-140 was reported to be involved in the chemoresistance of osteosarcoma cells via the suppression of histone deacetylase [4], which in turn reduced cell proliferation [32]. [score:3]
Inhibition of miR-140-5p ameliorated the anticancer drug -induced cell proliferation decrease in vitro. [score:3]
As shown in Figures 2(A) and 2(B), transfection with miR-140-5p inhibitor gave rise to a marked increase in sensitivity after treatment with 60 and 80 μM Cis in the Saos-2 and MG-63 cell lines. [score:3]
To determine the possible contribution of miR-140-5p to autophagy in drug -treated osteosarcoma cells, miR-140-5p expression was manipulated in Saos-2 cells via transfection with miR-140-5p mimics or miRNA control. [score:3]
Inhibition of miR-140-5p promotes the anticancer drug -induced cell proliferation decrease. [score:3]
Our next goal was to identify targets of miR-140-5p that influence autophagy. [score:3]
In addition, significantly higher conversion levels of LC3-I to LC3-II and decreased expression levels of p62 were also confirmed in the osteosarcoma cells transfected with miR-140-5p mimics (P<0.05 respectively; Figures 3D– 3F). [score:3]
Thus, the expression level of miR-140-5p was quantified in Saos-2 and MG-63 cells following treatment with Dox or Cis. [score:3]
Overexpression of miR-140-5p induces the activation of autophagy, which promotes tumour cell survival and chemoresistance. [score:3]
qPCR analysis showing the relative miR-140-5p expression to U6 in (A) Saos-2 and (B) MG-63 cells. [score:3]
The sequence of miR-140-5p inhibitor was 5′-AA CCC AUG GAA UUC AGU UCU CA-3′, and miR-NC was 5′-UCU ACU CUU UCU AGG AGG UUG UGA-3′. [score:3]
The effect of miR-140-5p overexpression was determined by real-time PCR shown in Figure 3(C). [score:3]
Quantification of miR-140-5p expression was conducted using the mirVana qRT-PCR miRNA Detection kit (Ambion), where U6 small nuclear RNA was used as an internal control, according to the protocol previously described [37]. [score:3]
The present study confirmed that during treatment with Dox or Cis in osteosarcoma cells, miR-140-5p expression was strongly induced. [score:3]
Therefore, miR-140-5p expression is induced in vitro during anticancer drug therapy in osteosarcoma cells. [score:3]
miR-140-5p was demonstrated to be the most highly-expressed miRNA. [score:3]
As shown in Figures 2(C) and 2(D), miR-140-5p in transfection resulted in a dose -dependent amelioration of 0.6 and 0.8 μg/ml Dox -induced cell proliferation inhibition in the Saos-2 and MG-63 cell lines. [score:3]
Thus, inhibition of miR-140-5p ameliorated the anticancer drug -induced cell proliferation decrease in osteosarcoma cells. [score:3]
To determine the possible effect of miR-140-5p on osteosarcoma cell proliferation, the proliferation of Saos-2 or MG-63 cells that had been treated with Dox or Cis and transfected with miR-140-5p inhibitors was determined using a CCK-8 assay. [score:2]
A quantitative PCR (qPCR) assay demonstrated that significantly higher expression levels of miR-140-5p were induced in Saos-2 or MG-63 cells following Dox or Cis treatment (Figures 1A and 1B). [score:2]
These mutant reporter constructs were then co -transfected along with miR-140-5p mimic into Saos-2 cells and reporter expression compared with wild-type reporter (Figure 4E). [score:2]
For GFP-LC3 dot number analysis, relative miR-140-5p expression, conversion of LC3-I to LC3-II, relative expression of p62 against GAPDH and CCK-8 measurements, the statistical evaluations are presented as the mean ± S. E. Data were analysed using the Student's t test. [score:1]
The sequence of miR-140-5p mimics was 5′-UGAGAACUGAAUUCCAUGGGUU-3′, and miR-control was 5′-UUC UCC GAA CGU GUC ACG UTT-3′. [score:1]
Saos-2 cells were transfected with either miR-control or miR-140-5p mimics. [score:1]
To validate the functionality of the putative miR-140-5p/ ip3k2 3′-UTR interaction, a reporter construct was prepared containing the full-length ip3k2 3′-UTR. [score:1]
At 24 h following transfection, the cells were subjected to 0.2 μg/ml Dox (Sigma–Aldrich) or 20 μM Cis (Sigma–Aldrich) for an additional 24 h. In a separate experiment, cells were simultaneously and additionally transfected with 20 nM miR-140-5p and analysed with fluorescence microscopy. [score:1]
These observations reveal a novel role for miR-140-5p in chemotherapy resistance during the treatment of osteosarcoma. [score:1]
The level of autophagy was determined in Saos-2 cells following miR-140-5p mimics transfection. [score:1]
To investigate if ip3k2 3′-UTR sequences can mediate regulation by miR-140-5p, we examined whether miR-140-5p directly reduces endogenous IP3k2 levels. [score:1]
In a separate experiment, ip3k2 mRNA levels were directly assayed by real time PCR after miR-140-5p mimics transfection. [score:1]
These findings identified the novel tumour stimulative role of miR-140-5p in IP3k2 -mediated autophagic chemotherapy resistance during the treatment of osteosarcoma. [score:1]
[1 to 20 of 63 sentences]
8
[+] score: 201
Results showed that miR-140 inhibition or miR-124 inhibition could upregulate the protein levels of iASPP, Cyclin D1 and CDK1, downregulated the protein levels of P21; XIST knockdown could downregulate the protein levels of iASPP, Cyclin D1 and CDK1, upregulate the protein levels of P21; the effects of miR-140 or miR-124 inhibitor on the indicated protein levels could be partially reversed by XIST knockdown (Figure 7A-7C). [score:21]
Results showed that in BxPC-3 and PANC-1 cells ectopic miR-140/miR-124 expression significantly downregulated XIST expression, while miR-140/miR-124 inhibition upregulated XIST expression (Figure 5E and 5F). [score:15]
Knockdown of XIST was achieved by infection of LV-sh-XIST (Genepharma, China); knockdown of iASPP was achieved by transfection of si-iASPP (Genepharma, China); forced iASPP expression was achieved by transfection of iASPP vector (Genepharma, China); p73 knockdown was achieve by anti-TP73 (Genepharma, China); forced p73 expression was achieved by pcDNA3.1/p73 (Genepharma, China); miR-140/miR-124 overexpression or inhibition was achieved by transfection of miR-140/miR-124 mimics or inhibitor (Genepharma, China) using Lipofectamine 2000 (Invitrogen, USA). [score:14]
We demonstrated that miR-140 inhibits PC cell proliferation through direct binding to iASPP [20]; consistent with our previous study, we observed that miR-140 inhibition upregulated iASPP, CDK1 and Cyclin D1 protein levels while downregulated P21 protein level. [score:12]
In PC tissues, miR-140, miR-124 and P21 expression was downregulated, while iASPP and CDK1 expression was upregulated. [score:11]
Results showed that miR-140, miR-124 and p21 mRNA expression was downregulated, while iASPP and CDK1 mRNA expression was upregulated in PC tissues compared with normal tissues (Figure 9A-9E). [score:10]
In our previous study, we demonstrated that miR-140 inhibits cell growth and invasion in pancreatic duct adenocarcinoma by targeting iASPP [20]; in addition, downregulation of miR-124 predicts poor prognosis in pancreatic ductal adenocarcinoma patients [21]. [score:8]
In LV-sh-XIST -transfected BxPC-3 and PANC-1 cells, the expression levels of miR-140 and miR-124 were significantly upregulated (Figure 5A and 5B). [score:6]
Results showed that the luciferase activity of wt-XIST and wt-iASPP 3’UTR vectors were significantly suppressed by miR-140/miR-124 mimics, increased by miR-140/miR-124 inhibitors; the changes of luciferase activity were abolished by mutations in miR-140 or miR-124 binding sites in XIST or the 3’UTR of iASPP (Figure 6E and 6F). [score:6]
In this study, we report an inverse dual regulation between X-inactive specific transcript (XIST) and miR-140/miR-124 which regulates PC cell proliferation and cell cycle through directly targeting iASPP. [score:6]
MiR-140/miR-124 mimics or inhibitor was transfected into BxPC-3 and PANC-1 cells to achieve miR-140/miR-124 overexpression or inhibition, respectively; the transfection efficiency was verified by using real-time PCR assays (Figure 5C and 5D). [score:6]
Next, the XIST expression in miR-140/miR-124 mimics- or inhibitor -transfected BxPC-3 and PANC-1 cells was determined by using real-time PCR. [score:5]
Figure 6 (A and B) A wt-XIST luciferase reporter gene vector, a mut-XIST vector containing a 4 bp mutation in the predicted binding site of miR-140, or a 6 bp mutation in the predicted binding site of miR-124, a wt-iASPP 3’UTR luciferase reporter gene vector, as well as a mut-iASPP 3’UTR vector containing a 6 bp mutation in the predicted binding site of miR-140, or a 5 bp mutation in the predicted binding site of miR-124 was constructed. [score:5]
A wt-XIST luciferase reporter gene vector, a mut-XIST vector containing a 4 bp mutation in the predicted binding site of miR-140, or a 6 bp mutation in the predicted binding site of miR-124, a wt-iASPP 3’UTR luciferase reporter gene vector, as well as a mut-iASPP 3’UTR vector containing a 6 bp mutation in the predicted binding site of miR-140, or a 5 bp mutation in the predicted binding site of miR-124 was constructed (Figure 6A and 6B). [score:5]
The indicated luciferase reporter gene vectors were co -transfected into PANC-1 cells with miR-140 mimics/miR-140 inhibitor (Figure 6C and 6D) or miR-124 mimics/miR-124 inhibitor (Figure 6E and 6F). [score:5]
MiR-140/miR-124 expression data was normalized to U6 small RNA expression. [score:5]
BxPC-3 and PANC-1 cells were co -transfected with LV-sh-XIST and miR-140 inhibitor or miR-124 inhibitor; then the protein levels of iASPP and cell cycle-related factors, P21, CDK1 and Cyclin D1 were determined by using Western blot assays (Figure 7A-7C). [score:4]
The expression levels of miR-140, miR-124, iASPP mRNA, CDK1 mRNA and p21 mRNA in PC tissues and their correlations with XIST. [score:3]
A schematic diagram showing XIST inhibits miR-140/miR-124 to promote pancreatic carcinoma growth through iASPP and cell cycle-related factors. [score:3]
Moreover, the effects of LV-sh-XIST on the indicated protein levels could be partially reversed by miR-140 or miR-124 inhibitor, respectively. [score:3]
Figure 5 (A) The expression of miR-140 in BxPC-3 and PANC-1 cells in response to XIST knockdown was determined by using real-time PCR assays. [score:3]
After cultured overnight, cells were co -transfected with the wild-type and mutated XIST or wild-type and mutated PPP1R13L 3’UTR reporter plasmid or pRL-TK plasmids and miR-140/miR-124 mimics or miR-140/miR-124 inhibitor. [score:3]
We also determined the expression levels of miR-140, miR-124, iASPP, CDK1 and P21 in PC tissues and adjacent normal tissues. [score:3]
XIST regulates cell cycle-related genes through miR-140/miR-124. [score:2]
XIST inversely mutual-regulates miR-140/miR-124. [score:2]
To further investigate the mechanism by which XIST affected the cell cycle of PC cells, we validated whether XIST could regulate miR-140/miR-124 expression. [score:2]
To investigate the mechanism by which XIST regulate iASPP and cell cycle-related gene expression, we focused on two PC cell proliferation-related miRNAs: miR-140 and miR-124 [20, 21]. [score:2]
We determined the expression levels of miR-140, miR-124, iASPP mRNA, CDK1 mRNA and p21 mRNA in PC tissues and adjacent normal tissues by using real-time PCR assays. [score:2]
XIST inversely mutual-regulates miR-140/ miR-124. [score:2]
MiR-140/miR-124 could directly bind to XIST and the 3’UTR of iASPP. [score:2]
To validate whether miR-140 and miR-124 were involved in XIST regulating PC cell cycle arrest through iASPP, we determined the protein levels of iASPP, CDK1, Cyclin D1 and P21. [score:2]
By using Wilcoxon’s paired test we compared the expression of miR-140, miR-124, iASPP and CDK1 in PC tissues and the paired adjacent normal colonic tissues. [score:2]
Figure 9 (A- E) The expression levels of miR-140, miR-124, iASPP mRNA, CDK1 mRNA and P21 mRNA in a large panel of 73 paired PC tissues and matched adjacent normal tissues were determined by using real-time PCR assays. [score:2]
We have demonstrated that knockdown of XIST induces cell cycle arrest at G0/G1 phase by regulating cell cycle-related genes in PC cell lines; given that miR-140/miR-124 could directly bind to XIST and the 3’UTR of iASPP, we then investigated whether/iASPP. [score:2]
Moreover, miR-140 and miR-124 could directly bind to XIST and the 3’UTR of iASPP, respectively. [score:2]
In PC cell lines, XIST and miR-140/miR-124 could inversely regulate each other, respectively. [score:2]
miR-140 and miR-124 were involved in this process through direct binding to XIST and the 3’UTR of iASPP. [score:2]
These data suggested that miR-140 and miR-124 were involved in the process of XIST regulating iASPP and cell cycle-related genes. [score:2]
These data suggested that XIST might regulate cell proliferation- and cell cycle-related genes through miR-140/miR-124. [score:2]
In RNA extracted from the precipitated AGO2 protein, we could detect XIST, miR-140/miR-124 and iASPP with a 1.8∼3-folds enrichment compared to IgG (Figure 6H), indicating that miR-140/miR-124 could directly bind to XIST and the 3’UTR of iASPP. [score:1]
We demonstrated that miR-140 binds to the 3’UTR of iASPP to attenuate PC cell growth and invasion capacity in our previous study [20]. [score:1]
Detection of AGO2 and IgG using Western blot (up); detection of XIST, miR-140/miR-124 and iASPP using qRT-PCR (low). [score:1]
Mature miR-140 and miR-124 expressions in cells was measured using a Hairpin-it TM miRNAs qPCR kit (Genepharma, Shanghai, China). [score:1]
XIST was positively related to iASPP and CDK1, inversely related to miR-140, miR-124 and P21, respectively. [score:1]
By using Spearman’s rank correlation analysis, we observed that XIST was inversely correlated with miR-140, miR-124 and p21, respectively, positively correlated with iASPP and CDK1, respectively (Figure 9E-9I). [score:1]
Here, we generated luciferase assays to investigate whether miR-140/miR-124 binds to XIST and iASPP to regulate their expression. [score:1]
[1 to 20 of 46 sentences]
9
[+] score: 165
These data suggest that IGFBP-5 is a direct target of miR-140, whereas miR-27a down-regulates, likely indirectly, both MMP-13 and IGFBP-5. This study is the first to show the regulation of these miRNAs in human OA chondrocytes. [score:9]
TGF-β significantly reduced miR-140 expression levels at the same time as strongly up -regulating IGFBP-5. Thus, TGF-β would act in two different ways to increase IGFBP-5: directly on its transcription, possibly at the promoter level, and indirectly by decreasing miR-140, a transcription inhibitor. [score:8]
Since several reports on miRNA profiling human cartilage [32], cancer [23] and general human tissues [21, 36] have already been published, we chose to follow up on MMP-13 and IGFBP-5 and focus our research on the expression and regulation of miR-140 and miR-27a, as these miRNAs were identified with high prediction by the five computational programs used as possible regulators of both MMP-13 and IGFBP-5 expression. [score:7]
Treatment with pre-miR-140 significantly inhibited (p = 0.0002) IGFBP-5 expression at as early as 24 hours (Figure 4A), while treatment with the anti-miR-140 significantly increased (p = 0.05) IGFBP-5 expression at 24 hours and 72 hours (p < 0.01) (Figure 4B). [score:7]
Data also suggest that miR-140 could act directly on decreasing IGFBP-5 expression but that miR-27a indirectly decreases both MMP-13 and IGFBP-5. These findings add another level of complexity to the overall regulation of MMP-13 and IGFBP-5, two factors involved in the OA pathological process. [score:6]
The present study showed that the IGFBP-5 gene expression is down-regulated by miR-140. [score:6]
To determine whether miR-140 and miR-27a could play a role in the OA disease process, we compared their expression levels between normal and OA chondrocytes and identified possible regulatory factors. [score:5]
Although data showed that miR-140 is a regulatory factor of IGFBP-5, this does not imply that it is the only factor to down-regulate IGFBP-5, as miR-140 is also decreased in OA. [score:5]
For comparison purposes, we also determined the expression of two other genes, IL-10 and bFGF, predicted as targets for miR-140 (bFGF) and miR-27a (IL10); these predictions were also obtained by the same five computational programs as described above. [score:5]
Transfection with pre-miR-140 significantly decreased (p = 0.0002) and with anti-miR-140 significantly increased (p = 0.05) IGFBP-5 expression at 24 hours, while pre-miR-27a did not affect either MMP-13 or IGFBP-5. Treatment with anti-miR-27a, but not with anti-miR-140, significantly increased the expression of both MMP-13 (p < 0.05) and IGFBP-5 (p < 0.01) after 72 hours of incubation. [score:5]
To this end, we used pre-miRNA and anti-miRNA molecules to determine the effects of miR-140 and miR-27a on the expression of target genes. [score:5]
We identified the miRNAs miR-140 and miR-27a as regulators of these two genes and studied their expression and regulation in normal and OA human chondrocytes. [score:5]
The results as illustrated in Figure 3 showed that treatment with pre-miR-140 or miR27a (Figure 3A) did not significantly affect MMP-13 expression levels, while transfection with anti-miR-27a (Figure 3B) increased MMP-13 expression with time, reaching statistical significance (p < 0.05) at 72 hours. [score:5]
Regulation of miR-140 and miR-27a expression levels inchondrocytes. [score:4]
Five computational algorithms identified miR-140 and miR-27a as possible regulators of MMP-13 and IGFBP-5 expression. [score:4]
There was a significant reduction (77%, p < 0.01) in miR-140 expression in OA compared to the normal chondrocytes, whereas miR-27a expression was only slightly decreased (23%). [score:4]
Figure 5 Expression and regulation of miR-27a and miR-140 levels in human chondrocytes. [score:4]
In contrast, miR-140 expression was significantly reduced (p < 0.01) in OA chondrocytes; a 77% reduction was found when compared to the expression in the normal cells. [score:4]
Because the cells were affected as early as 24 hours post-treatment, these data suggest that IGFBP-5 is a direct target of miR-140. [score:4]
OA chondrocytes were transiently transfected with pre- or anti-miRNAs specific for miR-140 and miR-27a and incubated for 24, 48 and 72 hours (gene expression) and 72 hours (protein production). [score:3]
Figure 3 Effect of pre- and anti-miR-140 and miR-27a on MMP-13 gene expression. [score:3]
The decreased expression of IGFBP-5 in OA is the outcome of the interplay between these factors in which miR-140 plays a role. [score:3]
Treatment with anti-miR-140 did not affect MMP-13 expression (Figure 3B). [score:3]
Figure 4 Effect of pre- and anti-miR-140 and -27a on IGFBP-5 gene expression levels. [score:3]
OA chondrocytes were transfected with pre-miRNA and anti-miRNA molecules specifically targeting the human miR-140 and miR-27a (45 nM final concentration; Applied Biosystems) in DMEM and the HiPerfect Transfection Reagent (3% final concentration; Qiagen). [score:3]
This could be explained by the fact that OA chondrocytes do not produce these cytokines at high levels [50], in addition to the slightly increased miR-140 expression following TNF-α treatment. [score:3]
Modulation of IGFBP-5, miR-140 and miR-27a expression was determined upon treatment of OA chondrocytes with cytokines and growth factors. [score:3]
Data revealed that both miRNAs are expressed in human OA chondrocytes at about the same level as the RNU24 control gene, which was given an arbitrary value of 1. Values of 0.88 and 0.94 fold change were recorded for miR-140 and miR-27a respectively. [score:3]
All together, these data suggest that miR-140 acts directly on IGFBP-5 and miR-27a acts indirectly on both genes. [score:3]
Tuddenham et al [29] reported the presence of miR-140 in cartilaginous tissues of the developing mouse and showed that this miRNA targeted the mouse histone deacetylase 4 mRNA. [score:3]
The expression levels of IGFBP-5, miR-140, and miR-27a were quantified by real-time polymerase chain reaction (PCR). [score:3]
None of the other factors tested affected miR-140 expression. [score:3]
Data show that TGF-β, known to be increased in OA cartilage [51, 52], is a candidate for the reduced expression of miR-140 in these cells. [score:3]
miR-140 expression was significantly reduced (p < 0.03) by TGF-β (Figure 5B); it was also reduced by BMP-2, although not quite reaching statistical significance. [score:3]
Interestingly, MMP-13 and bFGF, which were also predicted to be miR-140 targets, were not affected by this miRNA. [score:3]
This appears to be a direct effect, as IGFBP-5 is regulated as early as 24 hours post-treatment by the pre- and anti-miR-140. [score:3]
Our study is the first to show the regulation of the two miRNAs, miR-140 and miR-27a, in OA chondrocytes. [score:2]
However, because of the differential role of TGF-β in the regulation of IGFBP-5 and miR-140, the low level of IGFBP-5 in OA chondrocytes was surprising. [score:2]
Presence and effect of miR-140 and miR-27a in OA chondrocytes. [score:1]
Figure 2 Predicted recognition sequences for miR-140 and miR-27a in the 3'-UTR of the MMP-13 and IGFBP-5 mRNAs. [score:1]
The 3'-UTRs were analyzed by computational programs to predict the presence of functional miR-140 and miR-27a sites. [score:1]
Firstly, we investigated if miR-140 and miR-27a are expressed in human chondrocytes. [score:1]
We show that miR-140 levels are decreased in OA and that the decrease could be attributed to the growth factor TGF-β. [score:1]
A significant increase was noted in chondrocytes treated with anti-miR-27a (1.5 ± 0.2 fold increase, p < 0.05, n = 8), but treatment with anti-miR-140 or with the pre-miRNAs did not significantly affect MMP-13 production. [score:1]
For the four specimens in which the IGFBP-5 level was detectable, data showed that treatment with both anti-miR-27a and anti-miR-140 induced a marked increase in level and values of 2.0 ± 1.1 and 3.0 ± 1.0 fold increase respectively were recorded. [score:1]
All five computational programs predicted potential pairing sites for miR-140 and miR-27a in MMP-13 and IGFBP-5 3'-UTRs (Figure 2). [score:1]
[1 to 20 of 46 sentences]
10
[+] score: 162
Among the 77 miRNAs, 7 miRNAs, hsa-miR-33b-3p, hsa-miR-4284, hsa-miR-663a, hsa-miR-150-5p, hsa-miR-1233-3p, hsa-miR-671-3p, and hsa-miR-140-3p, were selected for further validation based on the fact that they were in the top 20 up- or downregulated miRNAs as found in microarray microRNA expression profiling presented in Fig.   1a, b. More specifically, miR-33b-3p and miR-4284 were among the top upregulated, and miR-663a, miR150-5p, miR-1233-3p, miR-671-3p, and miR-140-3p were downregulated. [score:12]
The expression levels of hsa-miR-33b-3p and hsa-miR-4284 coincided between the two methodologies, while hsa-miR-1233-3p, hsa-miR-140-3p, hsa-miR-150-5p, hsa-miR-663a, and hsa-miR-671-3p were marginally overexpressed in microarray analysis and appeared to be down-regulated with qRT-PCR Moreover, we found that hsa-miR-33b-3p and hsa-miR-4284 expression levels coincided between microarray analysis and qRT-PCR, exhibiting decreased expression in serum of OA samples compared to controls. [score:11]
The expression levels of hsa-miR-33b-3p and hsa-miR-4284 coincided between the two methodologies, while hsa-miR-1233-3p, hsa-miR-140-3p, hsa-miR-150-5p, hsa-miR-663a, and hsa-miR-671-3p were marginally overexpressed in microarray analysis and appeared to be down-regulated with qRT-PCR Moreover, we found that hsa-miR-33b-3p and hsa-miR-4284 expression levels coincided between microarray analysis and qRT-PCR, exhibiting decreased expression in serum of OA samples compared to controls. [score:11]
Hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-150p were significantly downregulated in serum samples of OA patients compared to healthy individuals Among the 2549 miRNAs tested using the Agilent 8 × 60 K miRNA-array platform, a total of 279 miRNAs were found to be differentially expressed (205 upregulated and 74 downregulated) (FDR < 0.008, p < 0.05) in the serum of OA patients compared to healthy individuals (Fig.   1a, b ). [score:10]
Among these, INSR and IGF1R were targeted by all three miRNAs, while ADCY7, VANGL1, WNT5A, PPP3R2, TGFBR1, FZD4, BRAF, and CREB5 were co -targeted by hsa-miR-140-3p, and hsa-miR-671-3p, RPTOR, CDKN1A, PRKCB, ADCYA1, PDPK1, MAPK1, ADCY2, TCS1, Kras, CBL, CHRM3, SGL1, CREB1, KCNN3, PRKC1, PPP2R5E, and KCNJ11 were co -targeted by hsa-miR-33b-3p, and hsa-miR-140-3p and KCNN1 were co -targeted by hsa-miR-671-3p and hsa-miR-33b-3p. [score:9]
Disease Association Annotation in our study revealed that among the differentially expressed miRNAs, hsa-miR-140-3p was involved in arthritic diseases. [score:7]
Fig. 4 Venn diagram of common target genes between miR-140-3p, miR-33b-3p and miR-671-3p Pathway enrichment analysis (Additional file  2: Table S2) revealed that the target genes of hsa-miR-140-3p, hsa-miR-33b-3p,and hsa-miR-671-3p are potentially involved in 48 common signaling pathways, including thyroid hormone synthesis, FoxO signaling pathway, insulin secretion, chemokine signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway, regulation of lipolysis in adipocytes, glucagon signaling pathway, and calcium signaling pathway, whereas 40 common pathways were predicted common between miR-140-3p and miR-33b-3p, such as mTOR signaling pathway, osteoclast differentiation, Ras signaling pathway, type II diabetes mellitus, adipocytokine signaling pathway, thyroid hormone signaling pathway, insulin signaling pathway, insulin resistance, sphingolipid signaling pathway, sphingolipid metabolism, and ErbB signaling pathway. [score:6]
We, next, validated with qRT-PCR, which offers high accuracy, sensitivity, and dynamic range [46] the expression levels of 7 selected out of the 77 DE miRNAs, which were among the top 20 up- or downregulated in the microarray screening, namely, hsa-miR-33b-3p, hsa-miR-4284, hsa-miR-663a, hsa-miR-150-5p, hsa-miR-1233-3p, hsa-miR-140-3p, and hsa-miR-671-3p, in serum and in OA and healthy articular cartilage samples. [score:6]
Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. [score:6]
Hsa-miR-663a, hsa-miR-150-5p, hsa-miR-1233-3p, hsa-miR-140-3p, and hsa-miR-671-3p, which were marginally over-expressed in microarray analysis, appeared to be downregulated with qRT-PCR. [score:6]
Fig. 4 Venn diagram of common target genes between miR-140-3p, miR-33b-3p and miR-671-3p Pathway enrichment analysis (Additional file  2: Table S2) revealed that the target genes of hsa-miR-140-3p, hsa-miR-33b-3p,and hsa-miR-671-3p are potentially involved in 48 common signaling pathways, including thyroid hormone synthesis, FoxO signaling pathway, insulin secretion, chemokine signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway, regulation of lipolysis in adipocytes, glucagon signaling pathway, and calcium signaling pathway, whereas 40 common pathways were predicted common between miR-140-3p and miR-33b-3p, such as mTOR signaling pathway, osteoclast differentiation, Ras signaling pathway, type II diabetes mellitus, adipocytokine signaling pathway, thyroid hormone signaling pathway, insulin signaling pathway, insulin resistance, sphingolipid signaling pathway, sphingolipid metabolism, and ErbB signaling pathway. [score:6]
Target gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that 28 genes were co -targeted by at least two miRNAs. [score:5]
Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. [score:5]
We found that three miRNAs, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, were significantly downregulated in the serum of OA patients compared to controls, and in addition, hsa-miR-140-3p and hsa-miR-671-3p were also significantly downregulated in OA compared to healthy articular cartilage (Figs.   3a, b and 6 ). [score:5]
Interestingly, our identified miRNAs included hsa-miR-140-3p, which participated in arthritis, joint diseases, and rheumatoid disease. [score:5]
Recently, it was shown that miR-140 is required for adipogenesis [51]and that decreased levels of miR-140 were found in the plasma of patients with morbid obesity influencing TGFbR1 expression levels [51], suggesting a new role of miR-140 in metabolic processes and obesity, main contributors in OA development. [score:4]
Tardif G Pelletier JP Fahmi H Hum D Zhang Y Kapoor M NFAT3 and TGF-beta/SMAD3 regulate the expression of miR-140 in osteoarthritisArthritis research & therapy. [score:4]
qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. [score:4]
On average, hsa-miR-140-3p was found to be downregulated in all OA samples. [score:4]
We identified a three-miRNA signature, including hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, which was downregulated in the serum of OA patients compared to controls and in silico predicted to be involved in regulating metabolic factors. [score:4]
Along the same thought process, another interesting finding in our study was that cAMP responsive element binding protein 5 (CREB5), co -targeted by hsa-miR-140-3p and hsa-miR-671-3p, was significantly enriched in insulin secretion and TNF signaling pathways. [score:3]
Hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-150p were significantly downregulated in serum samples of OA patients compared to healthy individuals To our knowledge, this is the first study to establish a potential global serum miRNA signature in OA patients using a high-resolution microarray technology interrogating 2549 miRNAs. [score:3]
An interesting finding in the in silico prediction analysis was that InsR and IGFR1 were common targets of all three hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671. [score:3]
Hsa-miR-140 plays an important role in cartilage homeostasis and chondrogenesis [47– 49] and has been previously reported with differential expression in OA cartilage [44, 50] but not in serum. [score:3]
Among these seven miRNAs, 3 miRNAs, hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p, were found significantly downregulated in OA serum samples compared to controls (p < 0.05) (Fig.   3a ). [score:3]
Hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p were significantly downregulated in serum samples of OA patients compared to healthy individuals. [score:3]
Biomarker Circulating miRNAs Hsa-miR-140-3p Hsa-miR-33b-3p Hsa-miR- 671-3p Metabolic miR-array Osteoarthritis Osteoarthritis (OA) is the most common chronic degenerative joint disease and a leading cause of pain and disability. [score:3]
Hsa-miR-1233-3p (a), hsa-miR-140-3p (b), hsa-miR-150-5p (c), hsa-miR-33-3p (d), hsa-miR-4284 (e), hsa-miR-663a (f), and hsa-miR-671-3p (g) manifested an area under the curve (AUC) value > 0.8 (AUC > 0.8) and p < 0.01 We verified by qRT-PCR the expression levels of the seven selected miRNAs (hsa-miR-33b-3p, hsa-miR-4284, hsa-miR-663a, hsa-miR-150-5p, hsa-miR-1233-3p, hsa-miR-140-3p, and hsa-miR-671-3p) in all serum samples. [score:3]
Furthemore, five pathways were predicted between miR-140-3p and miR-671-3p, including Wnt signaling pathway, endocrine and other factor-regulated, and calcium reabsorption (Fig.   5 ). [score:2]
All above suggest that the in silico predictions in the present study are highlighting the possible implication of circulating hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p as novel serum -based biomarkers for osteoarthritis prognosis and underlining their involvement in the regulation of metabolic processes that contribute to OA pathology. [score:2]
The expression levels of hsa-miR-140-3p, hsa-miR-150-5p, and hsa-miR-671-3p were significantly decreased in OA articular cartilage compared to healthy cartilage (p < 0.05) (Fig.   6 ). [score:2]
Fig. 5 Venn diagram of common signaling pathways between miR-140-3p, miR-33b-3p and miR-671-3p Based on the previous list of the revealed miRNAs, we further investigated their association with known diseases. [score:1]
The expression levels of 7 selected miRNAs screened with miRNA microarrays, as mature hsa-miR-33b-3p, hsa-miR-4284, hsa-miR-663a, hsa-miR-150-5p, hsa-miR-1233-3p, hsa-miR-140-3p, and hsa-miR-671-3p, were evaluated in serum samples from 12 OA patients and 12 healthy controls. [score:1]
[1 to 20 of 33 sentences]
11
[+] score: 132
Furthermore, the identification of specific miRNAs (miR-140 and miR-328) that regulate lung development, that show increased expression in lung epithelium as development progresses through saccular and alveolar stages, and that functionally suppress the Fgf9 3’ UTR, link Dicer1 activity to Fgf9 mRNA regulation. [score:9]
In hepatocellular carcinoma, miR-140 functions as a tumor suppressor, where it directly suppresses Fgf9 expression [42]. [score:8]
Although Fgf9 was not identified as a target of miR-140 in chondrocytes, FGF9 is known to functionally regulate bone growth in part by suppressing chondrocyte proliferation [38] and could therefore be a functional miR-140 target in developing bone. [score:8]
Collectively, expression patterns and in vitro suppression of the Fgf9 3’ UTR identified miR-140 and miR-328 as candidate miRNAs that could function in vivo to suppress Fgf9 as lung development progresses from pseudoglandular to canalicular stages. [score:8]
In non-small cell lung carcinoma, miR-140 suppresses tumor growth and metastasis by downregulating IGF1R [41], and in breast cancer, miR-140 targets Sox2 [44]. [score:8]
Analysis of expression of these miRs at different stages of lung development showed that miR-140-5p and miR-328-3p were expressed at relatively low levels during the pseudoglandular stage of lung development and at relatively higher levels during the saccular stage, while miR-182-5p showed the opposite profile (Fig 3B– 3D). [score:7]
Thus, miR-140 suppression of Fgf9 may not only be important for the development of lung and other tissues, but it may also function as an important tumor suppressor to ensure the quiescence of Fgf9 in adult tissues. [score:6]
Importantly, several of these miRNAs (miR-24, miR-140, miR-182, miR-183, miR-328) are expressed in fetal or neonatal lung and their relative expression levels are modulated during lung development [26, 27] or in lung cancer [28– 30]. [score:6]
Consistent with regulation of epithelial Fgf9 mRNA expression, miR-140 was prominently expressed in E12.5 lung epithelial ducts and E18.5 distal conducting airway epithelium and Type II pneumocytes (Fig 3H– 3M). [score:6]
These data indicated that during ex vivo lung development, miR-140 is sufficient to regulate Fgf9 expression in lung epithelium and regulate mesenchymal growth and epithelial branching. [score:6]
miRNA regulation of FGF9 We have shown that several conserved miRNAs can regulate the human and mouse FGF9 3’ UTR and that miR-140 regulates Fgf9 expression in developing lung. [score:6]
Our demonstration that miR-140 and miR-328 mimics can directly suppress the Fgf9 3’ UTR, shows the therapeutic potential of supplying critical microRNAs directly to lung epithelium during the period of childhood susceptibility to PPB. [score:5]
To establish whether miR-140 and miR-328 functionally regulate lung development, lung explant cultures were treated with seed -targeting 8-mer LNA oligonucleotides or single mismatch control LNA oligonucleotides (tiny LNAs) [31]. [score:5]
We have shown that several conserved miRNAs can regulate the human and mouse FGF9 3’ UTR and that miR-140 regulates Fgf9 expression in developing lung. [score:5]
MiR-140 and miR-328 regulate in vitro lung development and Fgf9 expression. [score:5]
Target sequences and probe design for analysis of miR-140 and miR-328 activity. [score:3]
At a concentration of 10 nM, tiny LNAs effectively blocked miR-140 or miR-328 ability to suppress Fgf9 3’ UTR activity in vitro (Fig 4A and 4B). [score:3]
We also show that the Fgf9 3’ UTR is responsive to conserved miRNA-140, miRNA-328, and miR-182, and that miRNA-140 (and miR-328) is an important regulator of lung development. [score:3]
miR-140 is contained within intron 16 of the ubiquitin ligase, Wwp2, which is expressed in chondrocytes and in epithelial tissues, including lung [36, 37]. [score:3]
To determine the primary cell-type expressing miR-140, we hybridized locked nucleic acid (LNA) in situ probes to E12.5 whole lungs and E18.5 lung sections. [score:3]
Of these, miR-140, miR-183, and miR-328 suppressed luciferase activity, while miR24 and miR-182 increased luciferase activity (Fig 3F, mouse, and S4A Fig and S4B Fig, human). [score:3]
The human and mouse FGF9 3’ UTR are highly conserved and are similarly regulated by miR-140, miR-182, miR-183, miR-328. [score:2]
Mature microRNA mimics for miR-24, miR-140, miR-182, miR-183, and miR-328 were then screened for their ability to regulate luciferase activity of the human or mouse FGF9 3’ UTR. [score:2]
Interestingly, miR-140 and Wwp2 are both directly induced by Sox9 in chondrocytes, ATDC5 cells, and 293T cells [37]. [score:2]
To establish specificity of miR-140, we engineered mutations in the mouse and human FGF9 3’ UTR miR-140 seed sequences. [score:2]
Using 6-FAM-labeled miR-140 tiny LNA, we also demonstrated efficient uptake into lung explant tissue 48 hr following exposure to media containing 100 nM tiny LNA (S6 Fig), consistent with efficient uptake of other types of oligonucleotides into lung explant cultures [21]. [score:1]
A mutant version of the Fgf9 3’ UTR, in which the miR-140 seed sequences was deleted, was generated using the QuikChange XL Site-Directed Mutagenesis kit (Agilent Technologies) using primers listed in S1 Table. [score:1]
miR-140 is also involved in the pathogenesis of several human malignancies, including breast, ovarian, non-small cell lung, basal cell, colon, osteosarcoma, and hepatocellular carcinoma [40– 46]. [score:1]
Repression of the Fgf9 3’ UTR by 10 nM miR-140 (A) or 10 nM miR-328 (B) transfected into HEK293 cells with a luciferase reporter construct containing a wild type mouse Fgf9 3’ UTR was blocked by adding 10 nM of the corresponding tiny LNAs to the culture medium. [score:1]
E12.5 lung was hybridized with a scrambled LNA in situ probe (H) or with the hsa-miR-140-5p LNA probe (I) (S2 Table). [score:1]
Histological sections from E18.5 wild type mouse lung were hybridized with a scrambled LNA in situ probe (L) or with hsa-miR-140-5p LNA probe (M). [score:1]
Mice that lack miR-140 are viable but exhibit decreased growth of long bones, attributed to reduced chondrocyte proliferation [35]. [score:1]
To demonstrate efficacy of tiny LNAs, HEK293 cells, transfected with pFgf9 UTR and miR-140 or miR-328 mimics, were co -transfected with tiny LNA antagomers. [score:1]
[1 to 20 of 33 sentences]
12
[+] score: 95
miRNA gene or target mRNA Species Genome variation Molecular effect PDGFRa Human Mutation 3′UTR Altered miR-140 bindingRattanasopha et al., 2012 miR-140 Human SNP Altered miRNA-140 processingLi et al., 2010, 2011 Zebrafish Overexpression Altred Pdfra repressionEberhart et al., 2008 MSX1 Human SNP 3'UTR Altered miR-3649 bindingMa et al., 2014 FGF2/5/9 Human SNP3'UTR Altered miR-496/miR-145/miR-187 bindingLi D. et al., 2016 miR-17-92 cluster Mouse Homozygous deletion Altered Tbx113, Fgf10, Shox2 & Osr1 repressionWang et al., 2013 miR-200b Mouse Overexpression Altered Smad2, Snail& Zeb112 repressionShin et al., 2012a, b miR-133b Zebrafish Overexpression UnkownDing et al., 2016 MiRNAs are small, 19–23 nucleotide non-coding RNAs that function as post-transcriptional repressors of gene expression, either through messenger RNA (mRNA) degradation or translational repression (Bartel, 2009). [score:14]
miRNA gene or target mRNA Species Genome variation Molecular effect PDGFRa Human Mutation 3′UTR Altered miR-140 bindingRattanasopha et al., 2012 miR-140 Human SNP Altered miRNA-140 processingLi et al., 2010, 2011 Zebrafish Overexpression Altred Pdfra repressionEberhart et al., 2008 MSX1 Human SNP 3'UTR Altered miR-3649 bindingMa et al., 2014 FGF2/5/9 Human SNP3'UTR Altered miR-496/miR-145/miR-187 bindingLi D. et al., 2016 miR-17-92 cluster Mouse Homozygous deletion Altered Tbx113, Fgf10, Shox2 & Osr1 repressionWang et al., 2013 miR-200b Mouse Overexpression Altered Smad2, Snail& Zeb112 repressionShin et al., 2012a, b miR-133b Zebrafish Overexpression UnkownDing et al., 2016 Using microarray analysis, the expression profile of murine miRNAs in the developing lip and PS were analyzed from E10 to E14 (Mukhopadhyay et al., 2010; Warner et al., 2014). [score:12]
miRNA gene or target mRNA Species Genome variation Molecular effect PDGFRa Human Mutation 3′UTR Altered miR-140 bindingRattanasopha et al., 2012 miR-140 Human SNP Altered miRNA-140 processingLi et al., 2010, 2011 Zebrafish Overexpression Altred Pdfra repressionEberhart et al., 2008 MSX1 Human SNP 3'UTR Altered miR-3649 bindingMa et al., 2014 FGF2/5/9 Human SNP3'UTR Altered miR-496/miR-145/miR-187 bindingLi D. et al., 2016 miR-17-92 cluster Mouse Homozygous deletion Altered Tbx113, Fgf10, Shox2 & Osr1 repressionWang et al., 2013 miR-200b Mouse Overexpression Altered Smad2, Snail& Zeb112 repressionShin et al., 2012a, b miR-133b Zebrafish Overexpression UnkownDing et al., 2016 CS, CC, JV: Conception of the work, drafting of the manuscipt, revision of the manuscript, final approval of the manuscript. [score:10]
The precise expression level of miR-140 is critical as overexpression will decrease Pdgfa -mediated attraction of both subsets of cNC cells while underexpression inhibits only the rostrally migrating cNC cells to move past the optic stalk. [score:9]
The minor, A allele of rs7205289, with a higher frequency in patients, was associated with a decrease of miR-140-5p expression and an increase of miR-140-3p expression. [score:5]
The zebrafish studies have also shown that miR-140 specifically targets pdgfra translation, which in turn represses Pdgfa -mediated attraction of both rostrally and caudally migrating anterior cNC cells to the palatal ectoderm. [score:5]
Interestingly, miR-140 also has its own regulatory element for SOX9, which suggest that its expression could be regulated independently of Wwp2. [score:5]
In addition, miR-140 was found to be down-regulated in palatal mesenchymal cells by smoking. [score:4]
In summary, miR-140 regulates the migration of neural crest cells, miR-200b regulates palatal fusion and the miR-17-92b cluster regulates palatal shelf growth. [score:4]
MiR-140 overexpression in zebrafish results in a cleft between the lateral elements of the ethmoid plate, a structural analog of the amniote palate that is found in higher vertebrates, while underexpression results in an abnormal shape of this plate (Eberhart et al., 2008; Dougherty et al., 2012). [score:4]
Studies in zebrafish have shown that proper miR-140 expression in migrating cNC cells is needed during palatogenesis. [score:3]
However, it is important to remember that miR-140 expression increases and is maintained in the developing PS up to and including the fusion of the secondary palate. [score:3]
In mice it has been identified that the transcription of both miR-140 and Wwp2 is regulated by the SOX9 transcription factor (Nakamura et al., 2011, 2012). [score:2]
Genetic evidence thus supports the role of miR-140 dysregulation in the etiology of cleft palate. [score:2]
MiR-140 is broadly expressed in migrating cNC cells and gradually becomes restricted to skeletogenic crest cells, including those of the PS (Eberhart et al., 2008; Li et al., 2011). [score:2]
In this respect, it is interesting to note that miR-140 null mice exhibit shorter palatal bones but no overt cleft palate (Miyaki et al., 2010), which mirrors the phenotype seen in zebrafish. [score:1]
MiR-140 as regulator of cranial neural crest (cNC) migration. [score:1]
Recent genetic studies have shown that miR-140 is also involved in the etiology of cleft palate in humans. [score:1]
MiR-140 is a highly conserved miRNA that is located in an orthologous intron of Wwp2, which encodes a ubiquitin ligase that is essential for palatogenesis (Nakamura et al., 2011). [score:1]
Single nucleotide polymorphism associated with nonsyndromic cleft palate influences the processing of miR-140. [score:1]
First, a genetic association study showed that a SNP (rs7205289:C>A) located in the precursor of miR-140 (pre-mir-140) contributes to non-syndromic cleft palate susceptibility by influencing the processing of miR-140 (Li et al., 2010). [score:1]
Apart from miR-140, the miR-17-92 cluster, and miR-200b (see below), most of the miRNAs have an as yet unknown role in palatogenesis. [score:1]
As zebrafish do not have a nasopharynx, secondary palate formation does not occur and, therefore, it is possible that miR-140 plays an additional role in secondary palate formation among higher vertebrates. [score:1]
A single base-pair substitution in the 3′UTR of PDGFRA was identified that is located only 10 base-pairs away from a predicted binding site for mir-140 (Rattanasopha et al., 2012). [score:1]
Sox9 is upstream of microRNA-140 in cartilage. [score:1]
MicroRNA-140 plays dual roles in both cartilage development and homeostasis. [score:1]
[1 to 20 of 26 sentences]
13
[+] score: 75
Over -expression of miR-520d, miR-101, miR-140, miR-485 and miR-448 in different T-ALL cell lines resulted in down-regulation of TAL1 transcript (Figure 4A) and/or protein (Figure 4B-4C) expression levels in a range of 20-60%. [score:8]
On the other hand, the fact that miR-140-5p is up-regulated in the different thymocyte subpopulations as compared to CD34+ cells may suggest that miR-140-5p could be part of the regulatory network that prevents TAL1 expression in normal committed thymic progenitors. [score:6]
Figure 6 A. Expression of miR-101, miR-520d-5p, miR-140-5p and miR-448 was determined by qRT-PCR and normalized to SNORD38B expression in TAL1 -positive (SUP-T1, CCRF-CEM, TAIL7, PF-382) and TAL1 -negative (HPB-ALL, P12-ICHIKAWA, TALL-1) T-ALL human cell lines. [score:5]
A. Expression of miR-101, miR-520d-5p, miR-140-5p and miR-448 was determined by qRT-PCR and normalized to SNORD38B expression in TAL1 -positive (SUP-T1, CCRF-CEM, TAIL7, PF-382) and TAL1 -negative (HPB-ALL, P12-ICHIKAWA, TALL-1) T-ALL human cell lines. [score:5]
Down-regulation mediated by these miRNAs in the TAL1 transcript was observed for miR-520d, miR-101, miR-140 and miR-448 in PF-382 cells and for miR-520d and miR-140 in SUP-T1 cells (Figure 4A). [score:4]
Moreover, T-ALL patient samples expressed lower levels of miR-101, miR-140-5p, miR-448 and miR-485-5p as compared to normal bone marrow cells (Figure 6C), which still express TAL1 (data not shown). [score:4]
Finally, the mutation of one of the three MREs for miR-140-5p (Figure 2D) was sufficient to restore luciferase expression (Figure 3D). [score:4]
Subsequently, we compared the expression of the miRNAs between TAL1 -positive and -negative T-ALL cell lines and verified that they were (miR-101, 520d-5p) or tended to be (miR-140-5p and miR-448; not reaching statistical significance), more expressed in the TAL1 -negative cell lines. [score:4]
Mutation of the two putative binding sites for miR-140-3p in the TAL1 3′UTR (Figure 2E) did not significantly affect reporter activity (Figure 3E), showing that the miR-140-3p is not the specimen responsible for the effect of miR-Vec-140 on the reporter expression. [score:4]
While we have not explored this possibility in the current manuscript, we note that even if such transcripts prevail in T-ALL cases, the most upstream canonical poly-adenylation site would only protect the MRE corresponding to miR-520-3p, miR-140-3p (both of which we showed to have no effect on reporter expression recovery upon mutagenesis assays) and the 4th MRE for miR-520-5p, which we showed that, together other two MREs for miR-520-5p, is not sufficient to recover the reporter expression. [score:4]
The miR-140-5p has also been associated with suppression of tumorigenesis in osteosarcoma and in colon [53], breast [54], lung [56] and hepatocellular [55] carcinoma. [score:3]
Whether and how regulation of any of these genes by miR-101 and miR-140-5p is biologically relevant for thymocyte development and leukemogenesis, and may complement effects on TAL1, has not been addressed so far. [score:3]
VEGF and HDAC4 are miR-140-5p predicted targets. [score:3]
Interestingly, miR-101 [20, 43- 52], miR-140-5p [53- 56], miR-520-5p [57], and miR-485-5p [58- 60], are all reported as putative tumor suppressors in different cancers. [score:3]
For further analysis we selected microRNAs that significantly lowered the luciferase expression in 25-50%: miR-101, miR-520d-5p, miR-140-5p, miR-448 and miR-485-5p (see Figure 2 for miRNA binding details). [score:3]
In agreement, we found that miR-101 and miR-140-5p were less expressed in T-ALL patient samples than in more differentiated thymocytes (Figure 6B). [score:3]
Details of binding of A. miR-101; B. miR-520d-5p and D. miR-140-5p to TAL1 3′UTR are depicted according to DianaMicroT [71] target prediction algorithm. [score:3]
Figure 2Details of binding of A. miR-101; B. miR-520d-5p and D. miR-140-5p to TAL1 3′UTR are depicted according to DianaMicroT [71] target prediction algorithm. [score:3]
The miRNAs miR-520-3p C. and miR-140-3p E. are not predicted to bind to TAL1 3′UTR, nevertheless the putative MRE were mutated as depicted. [score:1]
This demonstrated that these elements are true recognition sites for miR-140-5p in the TAL1 3′UTR. [score:1]
Results were normalized to scramble (SCR) miRNA on WT TAL1 3′UTR: A. miR-101, B, C. miR-520d, and D, E. miR-140. [score:1]
[1 to 20 of 21 sentences]
14
[+] score: 71
TargetScan predicted a total of 190 unique targets of canonical miR-140-3p and 317 unique putative targets of isomiR#3 (Fig.   3B). [score:7]
Third, some of the isomiRs of miR-140-3p (e. g. isomiR#3 in Fig.   3) showed differential expression in disease condition as well as upon treatment with IL-1β. [score:5]
Figure  3B shows the comparison of the targeting potential of the canonical miRNA versus the most abundant isomiR (#3) of miR-140-3p using TargetScan and DIANA-microT tools. [score:5]
First, miR-140-3p instead of −5p was the major expressed arm with 20-fold higher expression compared to miR-140-5p. [score:4]
Interestingly, miR-140-3p, that has been shown previously as the most abundant miRNA expressed in un-passaged primary human chondrocytes [16] and miR-140 locus has been shown to have significant impact on OA development [17], showed the maximum number of isoforms (17 in total). [score:4]
Conversely, cartilage-specific overexpression of miR-140 resulted in protection from antigen -induced arthritis [38]. [score:3]
In our study, we did not find any significant change in the expression of most of the isomiRs, both based on the origin of the chondrocytes, from normal subjects or OA patients, and upon treatment with IL-1β except for certain isoforms of miR-140-3p (discussed later). [score:3]
In silico analysis to check the effect of the seed-modifying 5′- deletion in isomiR#3 predicted a significant change in the putative mRNA targets of miR-140-3p. [score:3]
A number of the top expressing miRNAs, such as miR-27b-3p and miR-140-3p, have been extensively studied in the context of chondrocyte function and OA pathogenesis 17, 21. [score:3]
Based on the expression level, the canonical miR-140-3p was ranked 7 [th] among all the sequence variants of this miRNA. [score:3]
We also tested whether 5′ deletion in isomiR#3 resulting in the seed shift of the canonical miR-140-3p will impact its binding ability to its target mRNA sequences. [score:3]
Figure  3C shows the pathway enrichment analysis using miRPath v. 3/Diana tools highlighting the pathways potentially affected due to the change in targeting potential of the canonical miRNA-140-3p and isomiR#3. [score:3]
Interestingly, Crowe et al. found miR-140-3p to be the most abundant microRNA among all the chondrocyte-expressed microRNAs. [score:3]
Our results showed several interesting aspects of the expression of miR-140 locus in primary human chondrocytes. [score:3]
Miyaki et al. reported that knocking out microRNA-140 in mice led to a higher predisposition to the development of age-related OA-like changes and increased cartilage destruction in surgically -induced OA [38]. [score:3]
Second, miR-140-3p showed the highest number (n = 17) of isomiRs and many of which showed higher expression compared to the archetype sequence. [score:2]
miRNA-140 is the most studied microRNA to date with respect to chondrogenesis, cartilage homeostasis and the development of OA 13, 37, so much so that it is now being called as cartilage/chondrocyte-specific microRNA. [score:2]
Fourth, along with being expressed at high levels in primary chondrocytes, miR-140-3p and its isomiRs were among the highly enriched miRNAs in these cells but did not show a differential enrichment in cells treated with IL-1β compared to untreated controls. [score:2]
Figure  3A shows the individual modifications (isomiR #1 through #17) with ≥100 read counts in miR-140-3p aligned with the archetype miRBase sequence (#0). [score:1]
Since miR-140-3p showed the highest number of variants in our data set, we further focused on the analysis of the sequencing results of this miRNA. [score:1]
A limited number of miRNAs showed significant levels (>10%) of 3′ addition isomiRs, namely, miR-140, miR-148a, miR21, and miR-92a-1. Interestingly, miR-222 had most (97%) of the sequences in the form of 3′ addition isomiR. [score:1]
IsomiRs of miR-140-3p and effect of sequence variation on its function. [score:1]
This highlights a constitutive role of miR-140-3p and its isomiRs in the maintenance and homeostasis of human chondrocytes. [score:1]
The bio-informatic analysis in their study revealed significant differences in the targeting characteristics of their dominant miR-140-3p 5′ DEL U isomiR, that had the same nucleotide sequence as our dominant isomiR#3. [score:1]
Surprisingly, 5′ addition isomiR was limited to miR-140 only and accounted for 54% of the total miRNA pool of miR-140. [score:1]
AGO2-RIP-Seq Log2Fold (Control vs IL-1β), Q-value 1 mir-27b-3p 11Yes [21] −1, 1.43E-08 2 mir-10b-5p 2 No NS 3 let-7a-5p 9 No NS 4 mir-22-3p —Yes [43] NS 5 mir-26a-5p 5Yes [48] NS 6 mir-100-5p 14 No NS 7 let-7f-5p 18 No NS 8 mir-140-3p 1Yes [20] NS 9 mir-148a-3p —Yes [13] NS 10 mir-125a-5p — No NS 11 mir-21-5p 15Yes [13] NS 12 mir-199a-3p — No NS 13 mir-125b-5p 12Yes [13] NS 14 mir-222-3p —Yes [49] NS 15 let-7i-5p — No 1.01, 1.12E-23 16 let-7c-5p 17 No NS 17 mir-99b-5p 20 No NS 18 mir-92a-3p —Yes [50] 0.94, 4.87E-07 19 mir-99a-5p —Yes [51] NS 20 mir-92b-3p — No 1.35, 3.31E-09 NS, non-significant. [score:1]
Figure 3isomiRs of miR-140-3p and effect of sequence variation on its function. [score:1]
Similar to our results, Krawczynski et al. reported miR-140-3p as the miRNA showing the highest number (n = 14) of isoforms in the pig endometrium [39]. [score:1]
[1 to 20 of 28 sentences]
15
[+] score: 71
mRNA target prediction analysis of the reference mature miR-140-3p sequence using TargetScan revealed that this microRNA potentially regulates 240 different mRNA targets, whereas the miR-140-3p isomiRs harboring a 1-nt 5′ shift potentially regulates 367 mRNA targets. [score:11]
Redirection of the mRNA targeting abilities of 5′ shifted microRNAs, for which we used miR-140-3p as a proof-of-principle, is in accordance with a recent report in cardiomyocytes [47] and confirms the mRNA targeting specificity and functionality of the 5′ shifted platelet isomiRs. [score:6]
0050746.g006 Figure 6 (A) mRNA target prediction for the reference mature miR-140-3p sequence and the miR-140-3p isomiR harboring a 1-nt 5′ shift using TargetScan. [score:5]
Seven (7) mRNA targets that are predicted to be regulated by either miR-140-3p isoforms (Table S1) are present in platelets and are involved in platelet activation and degranulation, as referenced in the Gene Ontology (GEO) database. [score:4]
The blue X denotes the loss of base pairing of nt 2 of the miR-140-3p reference isoform, which may explain its lower efficiency in regulating CAP1 mRNA 3′UTR expression. [score:4]
Redirection of platelet miR-140-3p targeting upon a 1-nt shift of the 5′ cleavage site. [score:4]
As shown in Figure 6B (in blue), the reference miR-140-3p sequence had no regulatory activity on the Rluc reporter gene placed under the control of CAP1 3′UTR, which is consistent with TargetScan prediction. [score:4]
In contrast, the 1-nt shifted miR-140-3p isomiR significantly reduced reporter gene expression controlled by the CAP1 3′UTR element (Figure 6B, in red). [score:3]
The differential regulatory effects of the reference and 1-nt shifted miR-140-3p microRNAs may be explained by the CAP1 mRNA regulatory abilites conferred by pairing of nt 2 of the 1-nt shifted miR-140-3p isomiR. [score:3]
The expression level of the main isoforms of miR-140-3p are shown. [score:3]
In order to demonstrate the mRNA target specificity of the 1-nt shifted miR-140-3p, either forms of miR-140-3p were cotransfected with a reporter construct containing adenylate cyclase -associated protein 1 (CAP1) mRNA 3′UTR sequence inserted downstream of the Rluc reporter gene. [score:3]
0050746.g005 Figure 5 The expression level of the main isoforms of miR-140-3p are shown. [score:3]
Table S1 Platelet messenger RNA (mRNA) targets of the two main isoforms of miR-140-3p. [score:3]
Notably, only 50 of these mRNAs are predicted to be regulated by both forms of miR-140-3p. [score:2]
Notably, only 50 of these mRNAs are predicted to be regulated by both forms of miR-140-3p (Figure 6A). [score:2]
As exemplified with miR-140-3p, the most abundant sequences that match pre-microRNAs may represent an isomiR; here, the reference miR-140-3p sequence represents only a minority of the reads (Figure 5, in bold). [score:1]
HEK293 cells (2×10 [5]) were plated in 24-well plates 24 h before cotransfection with RNA duplexes encoding the reference miR-140-3p or the 1-nt 5′ shifted isomiR (0.2 to 20 pmol) and a psiCHECK (Promega) reporter construct (100 ng DNA) using Lipofectamine 2000. [score:1]
Base pairing complementarity between miR-140-3p microRNAs and their binding sites is shown in the upper panel. [score:1]
A binding site of perfect complementarity for both miR-140-3p isomiRs or the sequence of adenylate cyclase -associated protein 1 (CAP1) 3′UTR were inserted downstream of the Renilla luciferase (Rluc) gene of the psiCHECK reporter. [score:1]
HEK 293 cells were co -transfected with miR-140 microRNA duplexes, containing either the reference microRNA sequence (Reference) or the most abundant 1-nt 5′ shifted isomiR (Shifted), and a reporter gene construct in which the adenylate cyclase -associated protein 1 (CAP1) 3′UTR was inserted downstream of the Rluc reporter gene. [score:1]
Both miR-140 RNA duplexes generated functional miR-140-3p that could silence the activity of a Rluc reporter gene harboring a binding site perfectly complementary to either forms of miR-140-3p (Figure S5). [score:1]
Figure S5 Both the miR-140-3p reference sequence and its 1-nt 5′ shifted isomiR can silence Rluc reporter gene activity. [score:1]
The detected miR-140-3p isoforms were distributed as follows: 46% without a 5′ shift and 54% with a 1-nt 5′ shift. [score:1]
As shown on the left, most of the miR-140-3p isoforms may result from a combination of imprecise processing by Drosha and/or Dicer, including the most abundant, whose cleavage sites on the pre-microRNA species are shifted towards the 3′ end by a single nucleotide. [score:1]
Among them is miR-140-3p, which is one of the most abundant microRNA in platelets (please refer to Figure 2B). [score:1]
Of notice 2 major miR-140-3p isomiRs population coexist in platelets depending on 5′clivage by Dicer, either at the canonical position (blue bars) or harboring a 1 nt cleavage shift (red bars). [score:1]
[1 to 20 of 26 sentences]
16
[+] score: 68
These data indicate that miR-140 and miR-451 were able to downregulate luciferase expression by targeting the UTR sequences of var and therefore imply that both miR-140 and miR-451 can downregulate the expression of var group A genes and that miR-451 can also downregulate the expression of var group B genes. [score:18]
Among these miRNAs, miR-451 and miR-140 targeted the mRNAs of a critical parasite antigen, P. falciparum erythrocyte membrane protein-1 (PfEMP1), and downregulated its expression. [score:8]
Among these genes, miR-451 and miR-140 target the mRNA of a critical parasite antigen, PfEMP1, and downregulate its expression. [score:8]
Since the expression of PfEMP1 offers the parasite advantages in vivo, but not in vitro, the downregulation of PfEMP1 caused by miR-451 and miR-140 is unlikely to affect parasite development during in vitro culture, indicating that the function of human miRNAs against parasites is more complicated. [score:7]
39, 40, 41, 42, 43 Our data demonstrated for the first time that human miR-451 and miR-140 can recognize the 5′ or 3′UTR of var genes at the transcriptional level, effectively downregulating the expression of the luciferase reporter. [score:6]
In contrast to a control var group C gene PF3D7_0400400, both PF3D7_0712000 (var group A gene) and PF3D7_0800100 (var group B gene) could be downregulated by miR-140 and miR-451, respectively, although the regulation efficiency of the miR-140 mimic did not reach significance (Figure 4B). [score:5]
Luc-A exhibited significantly increased luciferase activity when co -transfected with a miR-140 inhibitor, whereas Luc-B and Down-A exhibited significantly decreased luciferase activity when co -transfected with a miR-451 mimic, in spite of inconsistent effects with miR-140 mimic and miR-451 inhibitors, possibly due to the interference of endogenous miRNAs in 293ET cells (Figure 4A). [score:5]
Taken together, our data suggest that, by mediating the transfer of hAgo2-miRNA complexes into iRBCs, host-derived miR-451 and miR-140 play a crucial role in regulating var gene expression during the blood stage of malaria infection. [score:4]
Among these miRNAs, we chose miR-451 and miR-140 for further studies because they were predicted to target the UTR of var genes (Supplementary Table S5), which encodes 60 homologs of PfEMP1 protein, a critical molecule in the adherence of iRBCs to the endothelium of host blood vessels in malaria patients. [score:3]
The sequences of miR-451 and miR-140 mimics or inhibitors are listed in Supplementary Table S4. [score:3]
In this study, we investigated the cargo transfer ability of RBC-derived MPs during in vitro culture of the asexual erythrocytic stages of P. falciparum, attempted to identify the miRNA complexes within the MPs, and studied the effects of two miRNAs, miR-451 and miR-140, on the expression of P. falciparum var genes. [score:1]
[1 to 20 of 11 sentences]
17
[+] score: 61
At basal conditions we observed that the expression levels of miR-27a, miR-140, and miR-146a were significantly downregulated in OA cell cultures in comparison to normal (p < 0.01), while miR-365 was upregulated in OA chondrocytes (p < 0.01). [score:9]
IGFBP-5 3’-UTR is also targeted by miR-140, which plays an important role in OA pathogenesis; in fact, as shown by several studies on chondrocyte cultures, its expression was downregulated in injured cells, especially after pro-inflammatory cytokine stimulation [19, 20]. [score:8]
Transfection experiments with mimic miR-140 demonstrated the inhibition of MMP-13 and IGFBP-5, while in miR-140 knockout mice a significant increase of ADAMTS-5 was detected, demonstrating that MMP-13, ADAMTS-5, and IGFBP-5 are miR-140 direct target genes [17, 39]. [score:7]
The positive effect of miR-140 upregulation is also accompanied by a significant decrease in the expression levels of MMP-13 and ADAMTS-5, well known as matrix-degrading enzymes implicated in cartilage degradation during OA damage [36, 37, 38]. [score:6]
The aim of this study was to evaluate if a cyclic HP could influence cell transcriptional activity, modifying miR-27a/b, miR-140, miR-146a/b, and miR-365 expression levels, which are responsible for the regulation of mRNA levels of their target genes, MMP-13, ADAMTS-5, IGFBP-5, and HDAC-4, in normal and OA chondrocyte cultures. [score:4]
Yang J. Qin S. Yi C. Ma G. Zhu H. Zhou W. Xiong Y. Zhu X. Wang Y. He L. MiR-140 is co-expressed with WWP2-C transcript and activated by SOX9 to target SP1 in maintaining the chondrocyte proliferation FEBS Lett. [score:4]
Nakamura Y. Inloes J. B. Katagiri T. Kobayashi T. Chondrocyte-Specific MicroRNA-140 Regulates Endochondral Bone Development and Targets Dnpep To Modulate Bone Morphogenetic Protein Signaling Mol. [score:4]
We detected a statistically significant up-regulation of miR-27a/b, miR-140, and miR-146a/b in OA chondrocytes (p < 0.01) immediately after pressurization (T0), compared to the unloaded controls. [score:3]
The purpose of this study was to investigate the possible effect of cyclic hydrostatic pressure (HP) (1–5 MPa, 0.25 Hz) on miR-27a/b, miR-140, miR-146a/b, and miR-365 expression levels, as well as on the mRNA levels of their target genes, MMP-13, ADAMTS-5, IGFBP-5, and HDAC-4, in human normal and OA chondrocyte cultures. [score:3]
At different time points following HP application (T12, T24, and T48), high significant levels of miR-27a, miR-140, and miR-146a gene expression were maintained (p < 0.01) in comparison to the corresponding load-free conditions. [score:3]
The consequence of mechanical stress on miR-140 regulation remained unknown. [score:2]
miR-140 could be considered a regulator of chondrocyte differentiation, bone development, and cartilage homeostasis. [score:2]
Miyaki S. Nakasa T. Otsuki S. Grogan S. P. Higashiyama R. Inoue A. Kato Y. Sato T. Lotz M. K. Asahara H. MicroRNA-140 is expressed in differentiated human articular chondrocytes and modulates interleukin-1 responses Arthritis Rheum. [score:2]
Tardif G. Hum D. Pelletier J. P. Duval N. Martel-Pelletier J. Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes BMC Musculoskelet. [score:2]
A significant increase of this miRNA level was induced by our pressurization system at all the analyzed time points, showing that miR-140 acts as a mechanical transduction modulator. [score:1]
Miyaki S. Sato T. Inoue A. Otsuki S. Ito S. Y. Yokoyama S. Kato Y. Takemoto F. Nakasa T. Yamashita S. MicroRNA-140 plays dual roles in both cartilage development and homeostasis Genes Dev. [score:1]
[1 to 20 of 16 sentences]
18
[+] score: 60
Comparison of the expression profiles showed that miR-30a was significantly up-regulated (p = 0.006), while miR-140 and let-7b were significantly down-regulated (p = 0.01 for both) in FF pools from patients with PCOS (n = 30) compared to women with normal ovarian reserve (n = 91) (Fig. 1A–C). [score:8]
We demonstrate, for the first time, that the expression of let-7b and miR-140 is significantly decreased whereas miR-30a is up-regulated in FF samples from patients with PCOS. [score:6]
MiR-140 plays a role as tumor suppressor and is down-regulated in breast cancer via ERα signaling 41. [score:5]
MiR-29a was significantly down-regulated and miR-140 overexpressed in FF pools from women who were stimulated with HP-hMG compared with those treated with r-FSH. [score:5]
These findings suggest that the modifications of ERα expression observed in PCOS might influence negatively miR-140 expression in ovarian follicles. [score:5]
We also found that total high dose of gonadotropins was associated with miR-140 up-regulation. [score:4]
Specifically, miR-29a expression was significantly decreased and miR-140 expression significantly increased in FF pools from women treated with highly purified human menopausal gonadotropin (HP-hMG) compared with patients who were stimulated with recombinant follicle-stimulating hormone (r-FSH) (p = 0.03; p = 0.02, respectively) (Fig. 3A). [score:4]
This probably reflects a potential dose-effect relationship of gonadotropins on FF miR-140 expression profile. [score:3]
The relative expression of the five miRNAs (let-7b, miR-29a, miR-30a, miR-140 and miR-320a) in each FF pool was calculated relative to that of miR-16 by using the equation 2 [−∆Ct], in which ∆Ct was determined by the formula: Ct target miRNA−Ct miR-16. [score:3]
Conversely, FF expression of miR-29a and miR-140 varied significantly according to the gonadotropin treatment. [score:3]
The AUC values for the individual performance of FF miR-30a, FF miR-140 and FF let-7b expression profiles in PCOS discrimination were 0.67 (0.57–0.76), 0.67 (0.57–0.76) and 0.67 (0.57–0.76) (p = 0.02, p = 0.007, p = 0.003), respectively (Fig. 2A–C, Table 2). [score:3]
As FF miR-30a, miR-140 and let-7b expressions were related to PCOS with a p-value lower than 0.05 in univariate analyses, they were integrated in the multivariate analysis. [score:3]
Moreover, whatever the type of gonadotropin, miR-140 was significantly up-regulated in FF pools from women who received higher total doses of gonadotropins (≥3000 IU/l) compared to those treated with lower doses (<3000 IU/l) (p = 0.03) (Fig. 3B). [score:3]
These results indicate that the combination of miR-30a, miR-140 and let-7b, which are differentially expressed in FF samples from patients with PCOS compared to women with normal ovarian reserve, gives the largest AUC value with high sensitivity and specificity, and suggest that these three miRNAs represent new potential PCOS biomarkers. [score:2]
This study investigated the expression profiles of five circulating miRNAs (let-7b, miR-29a, miR-30a, miR-140 and miR-320a) in FF pools from patients undergoing IVF/ICSI procedure. [score:1]
Moreover, the sensitivity and the specificity of FF miR-30a, FF miR-140 and FF let-7b were 57.7%, 57.7% and 53.9% and 85.1%, 81.1% and 75.7%, respectively (Table 2). [score:1]
Likewise, Spearman’s correlation analysis showed that FF miR-140 level was significantly and positively associated with the total dose of gonadotropins (r = 0.21; p = 0.02) (data not shown). [score:1]
[1 to 20 of 17 sentences]
19
[+] score: 57
Other miRNAs from this paper: hsa-mir-25, hsa-mir-221, hsa-mir-708
It is very likely that the inhibition of expression of chemokine genes following miR-708 or miR-140-3p transfection resulted from indirect mechanisms of decreased activation of transcription factors and MAP kinases as well as binding of miRNAs to cause translational repression and/or mRNA breakdown. [score:8]
The expression of many of the chemokine genes in HASM cells is regulated by signaling pathways that are downregulated by miR-140-3p. [score:7]
miR-140-3p transfection of HASM cells also resulted in inhibition of expression of chemokines that were sensitive to inhibition by miR-708, with the exception of CXCL12. [score:7]
Transfection of cells with miR-140-3p caused significant attenuation of expression of all the five chemokine genes examined, while exerting a selective inhibitory effect on the release of CXCL12 but not the other chemokines. [score:5]
HASM cells express miR-708 and miR-140-3p constitutively and TNF-α causes a significant reduction in their expression [51, 52]. [score:5]
[48– 50] Dysregulation of miRNA expression has been implicated in airway inflammation [48– 50], but the specific miRNAs (miR-140-3p and miR-708) controlling inflammation have not previously been reported. [score:4]
Chemokine mRNA expression and release from HASM cells following miR-140-3p transfection. [score:3]
miR-140-3p transfection and chemokine mRNA expression and release. [score:3]
Of the chemokines that were assayed, only CXCL12 release exhibited significant down-regulation of release in mimic miR-140-3p -transfected cells compared to release from cells transfected with the scrambled miR-140-3p oligonucleotides or from control cells at all time points examined (Fig 7). [score:2]
Our recent investigations also provided evidence for down-regulation of p38 MAP kinase and NF-κB activation in HASM cells following transfection with miR-140-3p [52]. [score:2]
Our earlier study showed that miR-140-3p decreases the activation of p38 MAP kinase and NF-κB in HASM cells. [score:1]
HASM cells derived from 3–5 donors were transfected with mimic or scrambled (Scr) sequence mimic of miR-140-3p followed by exposure to TNF-α (10ng/ml) to measure chemokine mRNA expression and chemokine release. [score:1]
Reagents used in the current study: DMEM from GIBCO-BRL (Grand Island, NY); rh-TNF-α from R&D Systems (Minneapolis, MN); TRIzol, SuperScript III reverse transcriptase, Opti-MEM [®] reduced serum medium and Lipofectamine [®] RNAiMax transfection reagent from Invitrogen Life Technologies (Carlsbad, CA); Brilliant lll Ultra-Fast SYBR Green qPCR Master Mix from Agilent Technologies Inc (Santa Clara CA); control oligo (scrambled sequence mimic) and miR-708 mimic (mature miR-708 sequence: 5’-AAGGAGCUUACAAUCUAGCUGGG-3’; mature miR-140-3p sequence: 5′-UACCACAGGGUAGAACCACGG-3′) from Dharmacon (Lafayette, CO); Tris-base, glucose, HEPES and other chemicals from Sigma Chemical Co. [score:1]
HASM cells were transfected with miR-140-3p mimic oligonucleotides or the scrambled control and then treated with TNF-α. [score:1]
Therefore, we measured the expression and release of chemokines in response to TNF-α following miR-140-3p transfection. [score:1]
In conclusion, this study demonstrates a profound anti-inflammatory effect of miR-708 and miR-140-3p in HASM cells stimulated with the inflammatory cytokine TNF-α. [score:1]
0150842.g007 Fig 7 HASM cells derived from 3–5 donors were transfected with mimic or scrambled (Scr) sequence mimic of miR-140-3p followed by exposure to TNF-α (10ng/ml) to measure chemokine mRNA expression and chemokine release. [score:1]
The decreased p38 MAP kinase activation following miR-140-3p transfection noted in our previous studies [59] may be involved in the attenuation of CXCL12 release in response to TNF-α. [score:1]
As well, miR-140-3p also has predicted binding sites at 3’UTR of CXCL12 and CXCL8. [score:1]
Since many of these chemokines are involved in the recruitment of inflammatory cells such as eosinophils, basophils, mast cells and T lymphocytes into the airways during allergic airway disease, we measured their release from cells stimulated with the inflammatory cytokine TNF-α and following transfection with miR-708 or miR-140-3p. [score:1]
used in the current study: DMEM from GIBCO-BRL (Grand Island, NY); rh-TNF-α from R&D Systems (Minneapolis, MN); TRIzol, SuperScript III reverse transcriptase, Opti-MEM [®] reduced serum medium and Lipofectamine [®] RNAiMax transfection reagent from Invitrogen Life Technologies (Carlsbad, CA); Brilliant lll Ultra-Fast SYBR Green qPCR Master Mix from Agilent Technologies Inc (Santa Clara CA); control oligo (scrambled sequence mimic) and miR-708 mimic (mature miR-708 sequence: 5’-AAGGAGCUUACAAUCUAGCUGGG-3’; mature miR-140-3p sequence: 5′-UACCACAGGGUAGAACCACGG-3′) from Dharmacon (Lafayette, CO); Tris-base, glucose, HEPES and other chemicals from Sigma Chemical Co. [score:1]
[1 to 20 of 21 sentences]
20
[+] score: 47
This supports the proposition that targeting miR-140, its regulators, or mRNA targets could improve survival outcomes by regulating stem cell formation [73]. [score:7]
Welch t-tests for differential expression using RPKM values, upper quantile normalised rates and TMM normalised levels all supported lower miR-320a and miR-140 expression in breast cancer patients. [score:5]
Of these potentially differentially expressed miRNAs, three (miR-191, miR-150 and miR-30d) were not supported after TMM testing, and only miR-320a and miR-140 were differentially expressed using upper quantile normalisation as well (Table 2). [score:5]
MiR-140 has also been found to suppress both the metastasis as well as the growth of tumours in patients with non-small cell lung cancer by targeting the insulin-like growth factor 1 receptor [77]. [score:4]
Previously, miR-140 down-regulation was linked to the promotion of cancer stem cell formation in basal-like early stage breast cancer [76]. [score:4]
For miR-140, the largest t-test p was <0.006 (TMM t-test = 2.93), and the effect size (d = 1.19) suggested high power (95%) to find changes in expression if present (Table 3). [score:3]
Interrogation of the miRNA results using RPKM adjustment alone would have yielded six differentially expressed miRNAs (miR-320a, miR-140, miR-30d, miR-22, miR-191, and miR-150). [score:3]
MiR-140 was also identified as dysregulated in the breast cancer blood samples with a 1.72-fold lower expression based on our sequencing data. [score:3]
RPKM and upper quantile normalised t-test p-values supported a lower miR-140 expression in the blood samples from breast cancer patients relative to healthy control group (p<0.001 and p = 0.002 respectively, Fig 1). [score:3]
These two miRNAs showed lower expression in the blood samples from breast cancer patients relative to the healthy control group: miR-320a had the highest fold-change of 2.30, and miR-140 one of 1.72 (Table 3). [score:3]
0137389.g001 Fig 1 The distribution of miR-320a and miR-140 upper quantile normalised expression levels between the breast cancer and control groups from Illumina reads. [score:3]
The distribution of miR-320a and miR-140 upper quantile normalised expression levels between the breast cancer and control groups from Illumina reads. [score:3]
MiR-140 was not evaluated using RT-qPCR because its ranked expression did not partition the groups as clearly as miR-320a. [score:1]
[1 to 20 of 13 sentences]
21
[+] score: 47
Chondrogenic culture conditions resulted in increased expression of miR-140 while miR-146a expression was suppressed (D–F). [score:7]
A similar auto-regulatory feedback mechanism has also been described for the regulation of miR-93 and downstream Osterix expression during osteoblast mineralization [3] as well as for miR-140 on TGF-β signaling through SMAD3 suppression [44]. [score:7]
Relative expression (RT-qPCR) of miR-140, miR-138 and miR-146a in epiphyseal and diaphyseal cell populations (A–C) and the effect of differentiation media on expression in diaphyseal cells (D–F). [score:5]
Foetal epiphyseal cells expressed higher levels of miRs including miR-140 and miR-138 reported to promote chondrogenesis [20]– [22] while diaphyseal cells expressed miRs including miR-210 and miR-93 previously reported to promote osteogenesis [3], [23], [39]. [score:5]
Thus, miR-140 has been identified as a cartilage specific miR capable of promoting chondrogenic differentiation by increasing the expression of RUNX2, a gene important in chondrocyte hypertrophic differentiation, through down -regulating HDAC4 [19], [20]. [score:4]
In addition, miR-140 has been linked to the regulation of SMAD3 dependent TGFβ pathway through down regulation of SMAD3 protein levels and thus to play a role in chondrocyte development [44]. [score:4]
Culture in osteogenic media failed to modulate the expression of miR-138, miR-140 and miR-146a (Figure 5D and E). [score:3]
miR-140 was expressed at a higher level in epiphyseal cells (A). [score:3]
In addition, the effects of osteogenic and chondrogenic media on the expression of miR-140, miR-138 and miR-146a were examined. [score:3]
Individual TaqMan assays confirmed the expression of the cartilage specific miR-140 and the anti-osteogenic miR-138 was higher in the epiphyseal cell populations (Figure 5A and B). [score:2]
The use of osteogenic media did not affect the expression levels of miR-140, miR-138 and miR-146a compared to culture in basal conditions (D–F). [score:2]
Various reports have already demonstrated the importance of miRs during SSC differentiation; miR-140, a cartilage specific miR [19], was reported as a positive effector of chondrogenesis through PDGF signaling in zebrafish [45]. [score:1]
miR-138 and miR-140, have previously been reported to have anti-osteogenic and pro-chondrogenic properties respectively [21], [24] and were found to display a higher expression in epiphyseal cell populations and thus selected for revalidation using individual TaqMan RT-qPCR assay to assess the consistency of data of the current study compared to current literature. [score:1]
[1 to 20 of 13 sentences]
22
[+] score: 45
Human bone marrow derived SSCs cultured in the presence of TGF-β3 exhibited significant upregulation in expression of miR-140-3p (7.36, 5.80-fold change) and miR-140-5p (43.11, 49.36-fold change) at day 14 and day 21 compared to the expression at day 0 (Fig. 2E,F). [score:7]
TGF-β3 treatment enhances the expression of chondrogenic associated marker genes, enhances chondrogenic associated histological staining and enhances the expression of chondrogenic associated miR-140-3p and miR-140-5p and decreases the expression of miR-146b in human bone marrow derived SSCs. [score:7]
TGF-β3 treatment enhanced chondrogenic marker genes expression and chondrogenic associated miR-140-3p and miR-140-5p expression and decreased miR-146b expression in human SSCs. [score:7]
Chondrogenic associated miR-140-3p (20.2-fold change) and miR-140-5p (24.8-fold change) expression were both found to be significantly up-regulated in cells treated with TGF-β3 (Fig. 1H–I). [score:6]
Data is presented as the median and interquartile quartile range of the fold change in SOX9 mRNA (A), AGCAN mRNA (B) COL2A1 mRNA (C), COL9A1 mRNA (D), miR-140-3p (E), miR-140-5p (F) and miR-146b (G) expression in human bone marrow derived SSCs cultured in the presence of TGF-β3 for up to 21 days relative to untreated control human bone marrow derived SSCs at day 0. mRNA and miRNA expression was analysed at even time points across 21 days at days 0, 7, 14 and 21. n = 6, *p < 0.05, **p < 0.01, ***p < 0.001, Friedman test with Dunn’s post-test. [score:5]
For instance, miR140 and miR-193b, both associated with chondrogenic development can also target Wnt and TGF-β signalling 34 35, pathways that interact with the SOX transcription factor family in chondrogenesis. [score:4]
Data is presented as the median and interquartile quartile range of the fold change in SOX9 mRNA (A), AGCAN mRNA (B) COL2A1 mRNA (C) COL9A1 mRNA (D), miR-140-3p (H), miR-140-5p (I) and miR-146b (J) expression in human bone marrow derived SSCs cultured in the presence of TGF-β3 for 21 days relative to untreated control bone marrow derived SSCs cultured in the absence of TGF-β3 for 21 days. [score:3]
Sox5 has also been shown to co-operate with Sox6 and Sox9 to induce chondrogenic associated miR-140 expression, with identification of a Sox5/Sox6/Sox9 response element in the upstream region of miR-140 32. [score:3]
Following samples were analysed for expression of either: miR-146b, miR-140-3p, miR-140-5p or miR-146a using TaqMan [®] MiRNA Assays (Table 2). [score:2]
Both miR-140-3p and miR-140-5p served as positive controls for chondrogenic differentiation 20. [score:1]
[1 to 20 of 10 sentences]
23
[+] score: 44
Notably, miR-140-5p, the best-described miRNA in cartilage to date, was found to be one of the most highly expressed (albeit not differentially-expressed) miRNAs in all three of the cartilage regions analyzed, thus providing additional confidence in the array data. [score:5]
It will also be interesting to determine expression levels of miR-140-3p and-5p in osteoarthritic cartilage given a recent report describing regulation of miR-140-3p by the inflammatory cytokine, TNF-α, in airway smooth muscle cells [64]. [score:4]
To date, miR-140 is the best-described miRNA in cartilage since it was identified as abundantly expressed and almost specific to cartilaginous tissues during zebrafish and mouse development [25], [26]. [score:4]
From Table 1 that lists the top thirty most highly-expressed miRNAs in PC, DC and HYP, miR-140-5p was found to be one of the most abundant regardless of the status of chondrocyte differentiation. [score:3]
We also detected expression of miR-140-3p in all three regions of developing cartilage, albeit at lower levels than miR-140-5p (∼18-22 fold less depending on the cartilage region; results not shown). [score:3]
This finding provides confidence in the array data since miR-140 is the best-described miRNA in cartilage to date and is known to be highly expressed and almost specific to cartilaginous tissues. [score:3]
These findings may also suggest that miR-140 expression patterns change as the cartilage growth plate matures. [score:3]
In addition to studies on miR-140, there is an increasing number of reports on expression and function of other miRNAs in vitro. [score:3]
Therefore, in addition to a role for miR-140 in regulating development and homeostasis of cartilage tissue [27], [28] additional functions (potentially distinct functions for the 5p and 3p strands) may exist in an inflammatory environment as found in osteoarthritic cartilage. [score:3]
Also, Miyaki et al detected the larger primary precursor form of miR-140 (pri-miR-140) in murine growth plate sections by in situ hybridization that includes both 5p and 3p strand; different expression patterns may be obtained by specifically detecting either the mature 5p or 3p strand in vivo. [score:3]
In our system, we did not detect significant differences in expression of miR-140 between precursor, differentiated proliferating and hypertrophic chondrocytes. [score:3]
Miyaki et al reported higher levels of miR-140 expression in proliferating chondrocytes of mature (post-natal day 10) murine growth plates compared to hypertrophic chondrocytes [27]. [score:2]
This suggests that both the 5p and 3p strands of miR-140 are functional and that their ratio levels could change depending on developmental time point. [score:2]
A role for miR-140 in regulating homeostasis of mature articular cartilage has also been proposed [27]. [score:2]
miR-140 null mice have been generated by two independent groups that reported craniofacial deformities and dwarfism due to defects in growth plate cartilage of long bones [27], [28]. [score:1]
[1 to 20 of 15 sentences]
24
[+] score: 41
In human ASM cells, human recombinant TNF-α-(rh-TNF-α) -induced CD38 expression is attenuated by miR-140-3p through both direct binding to the 3’ Untranslated Region (3’UTR) of CD38 as well as indirect mechanisms involving activation of p38 MAP kinase and the transcription factor NF-κB. [score:7]
Among the numerous potential CD38 3’UTR binding targets that we have identified, miR-708 and miR-140-3p [17] appear to play major roles in the regulation of CD38 expression in HASM cells. [score:6]
Since the target sites of these miRNAs are closely situated in the 3’UTR of CD38 transcript (see Figure  3A), we examined whether transfection of HASM cells with both miR-140-3p and miR-708 would amplify the inhibitory effect on enzymatic activity of CD38. [score:5]
In this study, we investigated the expression of miR-708, its potential additive role with miR-140-3p in the regulation of CD38 expression and the underlying mechanisms involved in such regulation in human ASM cells. [score:5]
We also observed that transfection of cells with both miR-140-3p and miR-708 has no additive or synergistic effects on CD38 enzymatic activity, suggesting that either miRNA is capable of independently regulating CD38 expression in HASM cells. [score:4]
Our previous studies have identified a role for miR-140-3p in the regulation of cytokine -induced CD38 gene expression and enzyme activity independent of miR-708 [17]. [score:4]
Co-transfection of HASM cell with miR-140-3p and miR-708 at 50 nM and 100 nM (equimolar concentrations) significantly inhibited CD38 enzymatic activity relative to cells transfected with scrambled sequence mimic. [score:3]
In this regard, we recently reported evidence for such regulation involving the microRNA (miRNA) miR-140-3p [17]. [score:2]
Figure 4 Effect of miR-708 in combination with miR-140-3p on ADP-ribosyl cyclase activity in NA-HASM cells. [score:1]
A: Predicted binding sites for miR-708 and miR-140-3p in 3’UTR of CD38. [score:1]
Note that no additive effect was observed in cells transfected with equimolar concentrations of miR-708 and miR-140-3p relative to miR-708 alone. [score:1]
Other miRNAs (miR-708 and miR140-3p) which showed ct values ranging from 20–30 (Figure  1A) were selected for further studies. [score:1]
MiRNAs miR-1272, miR-548, miR-208a, miR-1298, miR-708 and miR140-3p were predicted to bind to the CD38 3’UTR with high context score. [score:1]
[1 to 20 of 13 sentences]
25
[+] score: 36
Other miRNAs from this paper: dre-mir-140
If miR-140 has an additional function to repress hdac4 independent of pdgfra repression, it is possible that splice-inhibiting MO -induced down-regulation of hdac4 mRNA by MO could result in less target for miR-140, thus leading to the availability of excess of miR-140 that could repress other target genes, leading to palatal skeleton defects. [score:10]
Analysis with Microinspector [25] of the complete sequence of hdac4 identifies two potential targets for the microRNA miR-140: one target inside exon-3, and another target spanning the end of exon-11 and beginning of exon-12 (data not shown), of interest because of previous work showing a role of this microRNA in palatal patterning [14]. [score:7]
We recently reported that a prominent clefting of the zebrafish palatal skeleton results from loss of function mutation of platelet-derived growth factor receptor-a (pdgfra), and over -expression of the microRNA miR-140, which regulates the function of pdgfra[14]. [score:5]
In zebrafish, over -expression of the inhibitory micro -RNA miR-140 results in palatal skeleton reduction [14]. [score:5]
Although two potential targets for miR-140 were identified for hdac4, clearly, any mechanistic function of miR-140 inhibiting hdac4 requires experimental testing. [score:5]
MicroInspector [25] software was used to identify potential targets for the microRNA miR-140 in hdac4. [score:3]
miR-140 has also been identified as a repressor of Hdac4 in mouse [34], although Eberhart et al. (2008) did not identify any miR-140 binding sites in the 3′-UTR of zebrafish hdac4. [score:1]
[1 to 20 of 7 sentences]
26
[+] score: 35
Part of the bone-protecting role of miRNA-140 is also possibly attributed to its ability to suppress the expression of MMP-13 in chondrocytes in a negative-feedback regulatory circuit [95]. [score:6]
Silencing the expression of miRNA-140 in mice results in the establishment of an age-related mouse mo del of OA, where the aggrecan content in the cartilage matrix is decreased by the age of 12 months in miR-140−/− mice due to the derepression of the expression of ADAMTS5. [score:5]
Nakamura Y. Inloes J. B. Katagiri T. Kobayashi T. Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenetic protein signaling Mol. [score:5]
On the other hand, miR-140 -overexpressing transgenes are endowed with resistance to the development of arthropathy [94]. [score:4]
ADAMTS5 (aggrecanase) is a miRNA-140 target, which finds application in mo delling OA in animals. [score:3]
Another study demonstrated that in OA a prominent feature is the altered expression of two miRNAs, miRNA-140-5p and miRNA-455-3p [110]. [score:3]
On the other hand, miRNA-140 displays an almost chondrocyte-specific pattern of expression and controls pathways that are essential for unperturbed bone morphogenetic factor (BMP)/Smad signaling in an evolutionarily conserved manner, from mouse to zebrafish [111]. [score:3]
Tardif G. Hum D. Pelletier J. P. Duval N. Martel-Pelletier J. Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes BMC Musculoskelet. [score:2]
Miyaki S. Sato T. Inoue A. Otsuki S. Ito Y. Yokoyama S. Kato Y. Takemoto F. Nakasa T. Yamashita S. MicroRNA-140 plays dual roles in both cartilage development and homeostasis Genes Dev. [score:1]
Intriguingly, both miRNA-455-3p and miRNA-140-5p are derived from intronic miRNA precursors that reside within collagen type XXVII alpha 1 (COL27A1) and WW domain containing E3 ubiquitin protein ligase 2 (WWP2) locus), respectively [110, 111]. [score:1]
Certain OA-related miRNAs, i. e., miRNA-33a, miRNA-455-3p, miRNA-140, and miRNA-335-5p, are actually embedded within the intronic regions of human SREBP-2, COL27A1, WWP2, and MEST, respectively. [score:1]
Liang Z. J. Zhuang H. Wang G. X. Li Z. Zhang H. T. Yu T. Q. Zhang B. D. MiRNA-140 is a negative feedback regulator of MMP-13 in IL-1beta-stimulated human articular chondrocyte C28/I2 cells Inflamm. [score:1]
[1 to 20 of 12 sentences]
27
[+] score: 32
While miR-140-3p effects on downregulation of CD38 expression in human ASM cells are mediated via inhibition of p38 MAPK and NF- κB activation, the effects of miR-708 effects are via inhibition of JNK MAPK and PI3K activation, the latter by increased expression of PTEN. [score:12]
Although the target prediction resulted in the identification of several potential miRNA targets in the 3′UTR, quantitative RT-PCR showed expression of miR-140-3p and miR-708. [score:7]
The mechanisms by which miR-140-3p and miR-708 mediate the inhibitory effect on CD38 expression are different. [score:5]
In human ASM cells transfected with miR-140-3p or miR-708 mimics, CD38 mRNA expression and ADP-ribosyl cyclase activity were significantly attenuated compared to expression and enzyme activity in cells transfected with a control oligonucleotide. [score:4]
Exposure to TNF- α caused a reduction in the expression of miR-140-3p and miR-708 to a comparable magnitude in cells from asthmatics and nonasthmatics. [score:3]
In cells transfected with the miR-140-3p mimic, there was decreased TNF- α -induced activation of p38 MAPK and NF- κB. [score:1]
[1 to 20 of 6 sentences]
28
[+] score: 29
miR-19b-3p targets TIMELESS and NR1D2 and many of its correlated neighbours, let-7e-5p, miR-99b-5p and, indirectly, miR-140-3p (separated by 1 degree and connected via miR-214-3p and miR-212-3p) are instead down-regulated, suggesting a potential regulation of miR-19b-3p on these miRNAs. [score:8]
miR-19b-3p is correlated with miR-99b-5p, targeting PER1, RORA and TIMELESS mRNAs and, indirectly, with miR-140-3p, targeting NPAS2 and TIMELESS mRNAs. [score:6]
Besides, these miRNAs are involved in the pathways controlling cancer cell proliferation and invasiveness (Supplementary Table S6) Table 2 Fold Change (Tumor versus Control) Targets let-7e-5p Down PER1, CLOCK miR-125b-5p Down PER1, RORA, TIPIN miR-140-3p Down NPAS2, TIMELESS miR-99b-5p Down PER1, RORA, TIMELESS miR-19b-3p Up TIMELESS, NR1D2 miR-139-5p Down TIMELESS Figure 3 Multi-layer network of clock genes and targeting miRNAs in which nodes represent clock genes or miRNAs, while edges represent correlation or interaction among miRNAs or genes. [score:5]
Besides, these miRNAs are involved in the pathways controlling cancer cell proliferation and invasiveness (Supplementary Table S6) Table 2 Fold Change (Tumor versus Control) Targets let-7e-5p Down PER1, CLOCK miR-125b-5p Down PER1, RORA, TIPIN miR-140-3p Down NPAS2, TIMELESS miR-99b-5p Down PER1, RORA, TIMELESS miR-19b-3p Up TIMELESS, NR1D2 miR-139-5p Down TIMELESS Figure 3 Multi-layer network of clock genes and targeting miRNAs in which nodes represent clock genes or miRNAs, while edges represent correlation or interaction among miRNAs or genes. [score:5]
As illustrated in Table 2 and Figure 3, miR-125b-5p, miR-140-3p, let-7e-5p and miR-99b-5p are all down-regulated in tumor as compared to non-tumor tissues and all target clock genes. [score:5]
[1 to 20 of 5 sentences]
29
[+] score: 28
The most significantly down-regulated miRNA was hsa-miR-513b-5p, the most significantly up-regulated miRNAs was hsa-miR-140-5p, both with a p value of 3 × 10 [−13]. [score:7]
Among the miRNAs that showed largest concordance was miR-140-5p, the most significantly up-regulated miRNA in plasma was likewise significantly up-regulated in blood of endurance athletes (Fig.   4b). [score:7]
We observed significant variations in the abundance of miR-140-3p that is a known circulating disease markers (raw and adjusted p value of 5 × 10 [−12] and 4 × 10 [−7]). [score:3]
The respective part of the network is also presented in Fig.   6. VEGFA is targeted by five miRNAs, the previously mentioned miR-140-5p and also miR-378a-3p, miR-361-5p, miR-93-5p and miR-17-5p. [score:3]
b The second miR-140-5p is up-regulated in blood and plasma of strength as well as endurance athletes Taken together, our results suggest that miRNAs, preliminary measured from blood, are well suited to indicate the overall status of an athlete and whether the respective athlete is trained mostly towards endurance or strength. [score:2]
b The second miR-140-5p is up-regulated in blood and plasma of strength as well as endurance athletes Taken together, our results suggest that miRNAs, preliminary measured from blood, are well suited to indicate the overall status of an athlete and whether the respective athlete is trained mostly towards endurance or strength. [score:2]
In the latter publication another miRNA significantly affected in our study was described: miR-140-5p. [score:1]
MiR-140-5p in plasma was negative correlated to hemoglobin while plasma miR-188-5p was positive correlated to hemoglobin. [score:1]
Another study highlighted two miRNAs (again miR-140-5p as well as miR-532-5p) linked to type 2 diabetes that change with insulin sensitization [41]. [score:1]
Similarly, the levels of miR-140-5p and miR-650, both of which have been reported as makers for a wide range of human pathologies significantly depend on the training mode. [score:1]
[1 to 20 of 10 sentences]
30
[+] score: 27
Ten miRNAs were used for further in silico validation: one predicted by using above programs with elevated expression in microarray analysis (hsa-miR-574-3p; miRBase accession number: MIMAT0003239) and nine up-regulated in microarray analysis but not predicted by the algorithms used (hsa-miR-122, hsa-miR-199a-3p, hsa-miR-140-3p, hsa-miR-320a, hsa-miR-320b, hsa-miR-320c, hsa-miR-320d, hsa-miR-483-5p, hsa-miR-574-5p; miRBase accession numbers: MIMAT0000421, MIMAT0000232, MIMAT0004597, MIMAT0000510, MIMAT0005792, MIMAT0005793, MIMAT0006764, MIMAT0004761, MIMAT0004795, respectively). [score:6]
Although is hard to predict, which miRNA is involved in SERCA2 regulation, since the differentially expressed miRNA can be also from non-cardiomyocytes, we identified some good candidate miRNAs, which could be involved in the SERCA2 regulation (miR-199a for SERCA2b, miR-140 for both isoforms, and miR-574 for SERCA2a). [score:5]
In addition to miR-122, which was specifically expressed on present microarrays compared to our previous study [11] and is according to recent report down-regulated in plasma of patients with MI [27], miR-574 and miR-140 have not been yet described as involved in cardiovascular pathology. [score:5]
3121-142no −20.3−8.2−3.0789-810Partially (1, 3–6, 8) miR-574-3p−22.9−8.2−6.5347-368No −21.2−2.7−11.396-117no miR-574-5p−21.7−8.6−8.0263-285No −23.4−4.9−3.5479-501No −18.2−3.3−3.512-34No −20.5−9.00.3797-819Partially (1–5, 7) miR-140-3p−19.9−8.2−6.5348-368yes −20.5−9.9−3.5484-504No   −19.7 −8.7 0.3 799-819 no Using criteria postulated by Zhao et al. (2005) [18], we predicted binding sites in 3´-UTR of SERCA2b and SERCA2a mRNA for up-regulated miRNAs. [score:4]
3121-142no −20.3−8.2−3.0789-810Partially (1, 3–6, 8) miR-574-3p−22.9−8.2−6.5347-368No −21.2−2.7−11.396-117no miR-574-5p−21.7−8.6−8.0263-285No −23.4−4.9−3.5479-501No −18.2−3.3−3.512-34No −20.5−9.00.3797-819Partially (1–5, 7) miR-140-3p−19.9−8.2−6.5348-368yes −20.5−9.9−3.5484-504No   −19.7 −8.7 0.3 799-819 noUsing criteria postulated by Zhao et al. (2005) [18], we predicted binding sites in 3´-UTR of SERCA2b and SERCA2a mRNA for up-regulated miRNAs. [score:4]
Free-energy of binding and flanking regions (RNA22, RNAfold) was calculated for 10 up-regulated miRNAs from microarray analysis (miR-122, miR-320a/b/c/d, miR-574-3p/-5p, miR-199a, miR-140, and miR-483), and nine miRNAs deregulated from microarray analysis were used for validation with qPCR (miR -21, miR-122, miR-126, miR-1, miR-133, miR-125a/b, and miR-98). [score:3]
[1 to 20 of 6 sentences]
31
[+] score: 27
Comparing the inhibition of luciferase activity by the lentiviral expressed and endogenously expressed miRNAs, these results show that 1) the lentiviral expressed miR126 (both sense and antisense strands) and miR140 antisense strand exhibit potent RNAi activity; 2) the lentiviral expressed miR451 antisense strand does not have any RNAi activity; 3) the observed RNAi activity of lentiviral expressed miR21 (both sense and antisense strands) and miR140 sense strand could be due to endogenous miRNAs. [score:13]
Expression of both the sense and antisense strands of gga-miR21, gga-miR126 and gga-miR140 led to the inhibition of Renilla luciferase activity (Figure 2a). [score:5]
Based on literature reports and the miRNA database (miRBase), we chose four endogenous chicken miRNAs gga-miR21, gga-miR126, gga-miR140 and gga-miR451 that are expressed in many different tissues of adult chicken and chicken embryo [22]. [score:3]
As shown in Figure 2b, Renilla luciferase activity was inhibited by ∼98% by the sense strand of gga-miR21, ∼20% by the antisense strand of gga-miR21, and ∼60% by the sense strand of gga-miR140. [score:3]
Because gga-miR21, gga-miR126, gga-miR140 and gga-miR451 are generally expressed, we assayed their activity in DF-1 cells by directly transfecting the reporter plasmids into DF-1 cells. [score:3]
[1 to 20 of 5 sentences]
32
[+] score: 24
In order to check if the mRNA expression of these chemokines was negatively correlated with the up-regulation of all the corresponding targeting miRNAs (i. e., let-7a, miR-25, miR-23b, miR-26a, miR-132, miR-140, miR-146a, miR-146b, miR-155 and miR-210) identified in Table S2, we measured their levels using qRT-PCR. [score:6]
Figure 3 shows the relative expression levels of let-7a, miR-25, miR-26a, miR-132, miR-140, miR-146a and miR-155 at 3 and 6 h (panel A), and of five chemokines of their predicted targets at 12 and 24 h (panel B). [score:5]
Based on the observation that five chemokines (CCL2, CCL5, CXCL10, CXCL11 and CXCL12) are targeted by L. major-regulated miRNAs i. e., Let-7a, miR-25, miR-26a, miR-132, miR-140, miR-146a and miR-155, we show a negative correlation of transcript abundance with their corresponding miRNAs. [score:4]
Expression of let-7a, miR-25, miR-26a, miR-140, miR-146a and miR-155 at 3 h and miR-23b and miR-132 at 6 h post-infection of three healthy donors (D1, D2 and D3) is negatively correlated with CCL2, CCL5, CXCL10, CXCL11 and CXCL12 mRNA levels at 12 and 24 h post-infection in L. major-infected human macrophages. [score:3]
0002478.g003 Figure 3Expression means of let-7a, miR-25, miR-26a, miR-140, miR-146a and miR-155 at 3 h and miR-23b and miR-132 at 6 h post-infection of three healthy donors (D1, D2 and D3; panel A) is negatively correlated with CCL2, CCL5, CXCL10, CXCL11 and CXCL12 mRNA mean levels at 12 and 24 h post-infection (panel B) in L. major-infected human macrophages. [score:3]
Expression means of let-7a, miR-25, miR-26a, miR-140, miR-146a and miR-155 at 3 h and miR-23b and miR-132 at 6 h post-infection of three healthy donors (D1, D2 and D3; panel A) is negatively correlated with CCL2, CCL5, CXCL10, CXCL11 and CXCL12 mRNA mean levels at 12 and 24 h post-infection (panel B) in L. major-infected human macrophages. [score:3]
[1 to 20 of 6 sentences]
33
[+] score: 24
The significance of the differences in the expression was confirmed for four of the miRNAs, including three down-regulated miRNAs namely miR-181d-5p, miR-140-3p and miR-206 and one up-regulated miRNA namely miR-625-5p (P < 0.05) (Fig.   1). [score:9]
The significance of the differences in the expression was confirmed for four of the miRNAs, including three down-regulated miRNAs namely miR-181d-5p, miR-140-3p and miR-206 and one up-regulated miRNA namely miR-625-5p) (P < 0.05) (Fig.   2). [score:9]
In addition, we selected three miRNAs (miR-1233-3p, miR-140-3p and miR-421) with low or moderate expression levels in the three comparisons and miR-421 that had been identified in TOF [9]. [score:3]
For further analysis of the patient group, we additionally selected three miRNAs (miR-1233-3p, miR-140-3p and miR-421) with low or moderate expression levels in the three comparisons and miR-421 that had been identified in myocardial tissue of TOF patients [9]. [score:3]
[1 to 20 of 4 sentences]
34
[+] score: 23
Other miRNAs from this paper: hsa-mir-199a-1, hsa-mir-199a-2, hsa-mir-145
For instance, miR-145 directly targets Sox9 [68], whereas miR-140 shows expression variation parallel to those of Sox9 and Col2a1 and is induced by the abovementioned Sox trio [69, 70, 71] contributing to both development and maintenance of cartilage [72]. [score:7]
Given that miRNA (miR-140, -145 and -199a) expression levels, which have been reported to be involved in chondrogenic differentiation, are altered by IL-1β stimulation, changes in the miRNA network are also likely to be a mechanism by which inflammation suppresses chondrogenic differentiation [70, 91, 92]. [score:5]
Yang J. Qin S. Yi C. Ma G. Zhu H. Zhou W. Xiong Y. Zhu X. Wang Y. He L. MiR-140 is co-expressed with Wwp2-C transcript and activated by Sox9 to target Sp1 in maintaining the chondrocyte proliferation FEBS Lett. [score:4]
Yamashita S. Miyaki S. Kato Y. Yokoyama S. Sato T. Barrionuevo F. Akiyama H. Scherer G. Takada S. Asahara H. l-Sox5 and Sox6 proteins enhance chondrogenic miR-140 microRNA expression by strengthening dimeric Sox9 activity J. Biol. [score:3]
Miyaki S. Nakasa T. Otsuki S. Grogan S. P. Higashiyama R. Inoue A. Kato Y. Sato T. Lotz M. K. Asahara H. MicroRNA-140 is expressed in differentiated human articular chondrocytes and modulates interleukin-1 responses Arthritis Rheumatol. [score:2]
Miyaki S. Sato T. Inoue A. Otsuki S. Ito Y. Yokoyama S. Kato Y. Takemoto F. Nakasa T. Yamashita S. MicroRNA-140 plays dual roles in both cartilage development and homeostasis Genes Dev. [score:1]
Nakamura Y. He X. Kato H. Wakitani S. Kobayashi T. Watanabe S. Iida A. Tahara H. Warman M. L. Watanapokasin R. Sox9 is upstream of microRNA-140 in cartilage Appl. [score:1]
[1 to 20 of 7 sentences]
35
[+] score: 19
The cell type specific upregulated miRs (miR-520a-5p, -4271 and -4306 for hESCs and miR-140-3p, -210, -485 and -1271 for hMSCs) were predicted, or previously experimentally validated, to target HIF pathways inhibitors-HIF1AN and HIF3A while downregulated miRNAs (miR-138-5p, -92a-1-5p and miR-92a-2-5p in hESCs) were predicted to target HIF1A [56, 58]. [score:13]
This includes miR-138-5p, miR-140, miR-17-5p and members of miR-143/145 cluster as upregulated HRMs which have been described elsewhere as having a role in suppression of hMSCs differentiation [48– 51]. [score:6]
[1 to 20 of 2 sentences]
36
[+] score: 19
Moreover, miR-140-5p was found to contribute independently to explain fasting glucose variance after controlling for confounders, and it could be down-regulated by metformin and insulin [38]. [score:4]
SLC2A4RG was predicted as a target gene of miR-140-5p and has been found closely related to DM. [score:3]
were chosen from GO annotations in which target genes were significantly enriched (−log [10](P-value) > 5), which included hsa-miR-140-5p, hsa-miR-210, hsa-miR-362-5p, hsa-miR-590-3p, and hsa-miR-671-3p. [score:3]
The expression of miR-140-5p increases gradually with the increasing concentration of glucose in hyperglycemia -induced endothelial cells and was found to be involved in endothelial dysfunction [37]. [score:3]
The five potential candidate miRNAs (hsa-miR-140-5p, hsa-miR-210, hsa-miR-362-5p, hsa-miR-590-3p, and hsa-miR-671-3p) may be important factors related to BSS in DM and can be used as biomarkers for diagnosis and drug targets for treating DM with BSS. [score:3]
A cross-sectional study, which sought to identify the profile of circulating miRNAs in T2D and its response to changes in insulin sensitivity, found a significant increase of miR-140-5p in T2D patients. [score:1]
Their miRNAs were selected as the potential candidate miRNAs of BSS in DM, which were hsa-miR-140-5p, hsa-miR-210, hsa-miR-362-5p, hsa-miR-590-3p, and hsa-miR-671-3p (Table 4). [score:1]
Based on the analysis, it showed that five miRNAs were closely related to BSS in DM, including hsa-miR-140-5p, hsa-miR-210, hsa-miR-362-5p, hsa-miR-590-3p, and hsa-miR-671-3p. [score:1]
[1 to 20 of 8 sentences]
37
[+] score: 18
miR-140 expression is significantly decreased in human OA chondrocytes [16], thus favoring an increased expression of its target genes and consequently a role in cartilage degradation. [score:7]
Targeted deletion of miR-140 in mice resulted in age-related OA-like changes [17]. [score:3]
Of importance, miR-140 decreases the expression of genes known to play detrimental roles in OA cartilage. [score:3]
Miyaki S. Nakasa T. Otsuki S. Grogan S. P. Higashiyama R. Inoue A. Kato Y. Sato T. Lotz M. K. Asahara H. MicroRNA-140 is expressed in differentiated human articular chondrocytes and modulates interleukin-1 responses Arthritis Rheum. [score:2]
miR-140, which was originally found in cartilage, has been linked more specifically to OA [15, 16]. [score:1]
Miyaki S. Sato T. Inoue A. Otsuki S. Ito Y. Yokoyama S. Kato Y. Takemoto F. Nakasa T. Yamashita S. MicroRNA-140 plays dual roles in both cartilage development and homeostasis Genes Dev. [score:1]
Furthermore, more and more individual miRNAs, including miR-27b, miR-34a, miR-140, and miR-146a, have been linked to arthritis pathogenesis [6, 13, 14]. [score:1]
[1 to 20 of 7 sentences]
38
[+] score: 18
For expression studies, along with the 6 miRNAs, miR-140-5p which were shown to control the tumor metastasis in HNSCC and miR-181a-3p, an oral cancer-specific upregulated miRNA that was included as a background control to study lncRNA OIP5-AS1’s sponging activity. [score:6]
Jing P Sa N Xu W miR-140-5p affects the migration and invasion of hypopharyngeal carcinoma cells by downregulating ADAM10 expressionZhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. [score:6]
Out of the 8 selected miRNAs, miR-137, miR-140–5p, miR-148a-3p, miR-30a-5p and miR-338-3p were significantly downregulated in the tumors compared with normal tissue (P < 0.001, <0.001, 0.001, 0.001 and 0.0003, respectively) (Fig.   3a). [score:3]
miR-140-5p which has been shown to inhibit cell migration in hypopharyngeal carcinoma did not show any change with reference to tumor differentiation status [28]. [score:3]
[1 to 20 of 4 sentences]
39
[+] score: 17
Five miRNAs predicted to target Smad3 (miR-135a, miR-140-5p, miR-582-3p, miR-582-5p, and miR-938) were overexpressed, of which miR-140-5p has already been validated to target Smad3 directly [58]. [score:8]
Five miRNAs were upregulated (miR-140, miR-099a, miR-099b, miR-030b, and miR-030c) and only one (miR-138-2) was downregulated in macroadenomas compared to microadenomas. [score:6]
Thereby, the miRNAs targeting TGF- β signaling (miR-135a, miR-140-5p, miR-582-3p, miR-582-5p, and miR-938) may have effects in apoptosis [22]. [score:3]
[1 to 20 of 3 sentences]
40
[+] score: 17
Other miRNAs from this paper: hsa-mir-22, hsa-mir-122, hsa-mir-185
0024359.g002 Figure 2 A, Overexpression of miR122, miR140, and miR185 precursors suppressed activity of the corresponding reporters. [score:5]
A, Overexpression of miR122, miR140, and miR185 precursors suppressed activity of the corresponding reporters. [score:5]
Levels of endogenous mature miR122, miR22, miR140-5p,-3p, and miR185, which are expressed at relatively high levels in liver cells [16], were comparable in control and RACK1-knockdown cells (Fig. 3A and Figure S1). [score:4]
Transient knockdown of RACK1 reduced the function of three miRNAs: miR122, miR140, and miR185 (Fig. 2A). [score:2]
For example, the maturation of miRNAs used in our study, i. e., miR122, miR140, and miR185, is KSRP-independent [29]. [score:1]
[1 to 20 of 5 sentences]
41
[+] score: 17
Overexpression of miR-140-5p in 5637 cells (urinary bladder grade II carcinoma cells) attenuated cell migration and invasion and inhibited cell proliferation [48]. [score:5]
ΔNp63 | miR-140-5pp63 is another tumour suppressor protein belonging to the p53 family. [score:3]
none of European descent[61] hereditary spastic paraplegia type 31 miR-140 REEP1 c. 606+43G>T (T impairs G:U wobble base pairing) in silico: miRNA target prediction program. [score:3]
yes more than 80% white[60] hereditary spastic paraplegia type 31 miR-140 REEP1 c. 606+50G>A (A impairs G:U wobble base pairing) in silico: miRNA target prediction program. [score:3]
ΔNp63 | miR-140-5p. [score:1]
Analysis showed that the T allele is correlated with a decreased risk of bladder cancer because miR-140-5p is able to bind to the 3'-UTR of ΔNp63. [score:1]
10771) 48 Wang M et al. 2016 A functional variant in TP63 at 3q28 associated with bladder cancer risk by creating an miR-140-5p binding site. [score:1]
[1 to 20 of 7 sentences]
42
[+] score: 16
[179] In addition, some non-BMP-regulated miRNAs also have regulatory roles in BMP signaling: miR-141 and -200a remarkably modulate the BMP-2 -induced pre-osteoblast differentiation through the translational repression of Dlx5; [180] miR-542-3p targets BMP7 and represses BMP7 -induced osteoblast differentiation and survival; [181] miR-20a promotes osteogenic differentiation through upregulation of BMP/Runx2 signaling by targeting PPARγ, Bambi, and Crim1; [182] miR-140 targets a mild inhibitor of BMP Dnpep, and loss of miR-140 in mice causes growth defects of endochondral bones and craniofacial deformities. [score:16]
[1 to 20 of 1 sentences]
43
[+] score: 16
Several miRNAs are regulated by Sox9 (e. g. miR-140 and miR-455) [13– 15] or regulate Sox9 expression (e. g. miR-675 and miR-145) [16, 17]. [score:5]
Expression of miR-140-5p is also increased in OA in these samples, despite published data showing the converse and the increased susceptibility to OA in the miR-140 null mouse [8, 14]. [score:3]
These mice prematurely develop OA-like changes with age and are more susceptible to OA in the ‘destabilisation of the medial meniscus’ (DMM) mo del, whilst transgenic mice overexpressing miR-140 in cartilage were resistant to antigen -induced arthritis. [score:3]
Universal knockout of miR-140 lead to mild craniofacial deformities and dwarfism [8, 9]. [score:2]
MicroRNA-140, originally identified as a cartilage- and skeletal-restricted miRNA in zebrafish [6] and mouse development [7], is currently the best described miRNA in cartilaginous tissue. [score:2]
Since miR-140 has such a key role in cartilage homeostasis and osteoarthritis, it is likely that other miRNAs will show similar function as this is explored. [score:1]
[1 to 20 of 6 sentences]
44
[+] score: 16
In recent years, a putative role for miR-140 in the pathogenesis of OA was evidenced [11, 14, 43], since its expression is significantly reduced in OA tissue and that in vitro treatment of chondrocytes with IL-1ß, a cytokine involved in the pathogenesis of OA, suppresses miR-140 expression [46]. [score:7]
In our study, the expression levels of hsa-miR-140 and hsa-miR-146 in the microarray analyses showed no statistical significant differences when comparing healthy and OA samples. [score:3]
In previous reports hsa-miR-140 was down regulated and hsa-miR-146 was up regulated in OA cartilage [9, 12, 15]. [score:3]
However, hsa-miR-140 showed a tendency to be down regulated in OA and hsa-miR-146 showed a tendency to be up regulated in this pathology. [score:3]
[1 to 20 of 4 sentences]
45
[+] score: 15
In a comparison of the changes occurring in miRNA expression levels during the chondrogenesis of mesenchymal stem cells (MSCs) in vitro, it was discovered that the expression of miR-140 was significantly altered (7). [score:5]
Furthermore, chemokine ligand 12 and disintegrin and metalloproteinase with thrombosponin motifs were verified as direct targets of miR-140 (8). [score:4]
Another study on miR-140 demonstrated that equine cord blood-derived mesenchymal stromal cells expressed significantly higher levels of miR-140 after 14 days of chondrogenic differentiation (8). [score:3]
Furthermore, it was also discovered that miR-140 stimulated chondrogenesis in vitro by targeting Ras-related small GTPases (RALA) and thereby affecting SRY (sex determining region Y)-box (SOX)9 at the protein level (7). [score:3]
[1 to 20 of 4 sentences]
46
[+] score: 15
Evidence of the concerted interplay of miRNAs regulated by CpG-ODN and their potential target mRNAs was observed (Fig. 4) for 2 miRNAs upregulated (hsa-miR-302b and hsa-miR-374b) and for 13 miRNAs downregulated in CpG-ODN -treated mice (hsa-miR-135a, hsa-miR-136, hsa-miR-340, hsa-miR-445-5p, hsa-miR-424, hsa-miR-96, hsa-miR-142-3p, hsa-miR-140-5p, hsa-miR-542-3p, hsa-miR-18a, hsa-miR-18b, hsa-miR-101, and hsa-miR-99a). [score:10]
Comparison of hsa-miR-18a, hsa-miR-18b, hsa-miR-140-5p, hsa-miR-101, hsa-miR-556-3p, hsa-miR-424, hsa-miR-136, hsa-miR-340, hsa-miR-302b expression obtained by miRNA expression profile and qRT-PCR on tumors collected from human IGROV-1 ovarian tumor-bearing mice treated daily i. p. with CpG-ODN or saline (control group). [score:5]
[1 to 20 of 2 sentences]
47
[+] score: 15
It has been known that miR-140 [28] and miR-27 [30] negatively regulates MMP-13 expression indirectly by modulating NF-κB signaling or targeting BMP-7 and miR-27b binds directly with the 3’UTR of human MMP-13 mRNA [31]. [score:8]
Among miRNA analyzed, miR-23b, miR-30d, miR-132, miR-140-3p, miR-145, miR-150, miR-204 were up-regulated in OA chondrocytes whereas miR-22, miR-25, miR-26, miR-30c, miR-92b, miR-127, miR-194, miR-197, miR-296-5p, miR-342-3p, miR-488 were down-regulated in OA chondrocytes (Figure  1B). [score:7]
[1 to 20 of 2 sentences]
48
[+] score: 15
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-29a, hsa-mir-31, hsa-mir-99a, hsa-mir-100, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-192, hsa-mir-199a-1, hsa-mir-208a, hsa-mir-30c-2, hsa-mir-147a, hsa-mir-10a, hsa-mir-34a, hsa-mir-181b-1, hsa-mir-199a-2, hsa-mir-203a, hsa-mir-204, hsa-mir-217, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-200b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-125b-1, hsa-mir-132, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-146a, hsa-mir-150, hsa-mir-185, hsa-mir-193a, hsa-mir-195, hsa-mir-200c, hsa-mir-155, hsa-mir-181b-2, hsa-mir-30c-1, hsa-mir-219a-2, hsa-mir-296, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-302d, hsa-mir-374a, hsa-mir-375, hsa-mir-378a, hsa-mir-330, hsa-mir-328, hsa-mir-342, hsa-mir-325, hsa-mir-424, hsa-mir-429, hsa-mir-450a-1, hsa-mir-486-1, hsa-mir-146b, hsa-mir-497, hsa-mir-520e, hsa-mir-520f, hsa-mir-520a, hsa-mir-520b, hsa-mir-520c, hsa-mir-520d, hsa-mir-520g, hsa-mir-520h, hsa-mir-450a-2, hsa-mir-503, hsa-mir-608, hsa-mir-625, hsa-mir-629, hsa-mir-663a, hsa-mir-1271, hsa-mir-769, hsa-mir-378d-2, hsa-mir-675, hsa-mir-147b, hsa-mir-374b, hsa-mir-663b, hsa-mir-378b, hsa-mir-378c, hsa-mir-374c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-4661, hsa-mir-219b, hsa-mir-203b, hsa-mir-378j, hsa-mir-486-2
Furthermore, EGCG up-regulated miR-140-3p expression, which in turn was associated with the downregulation of aggrecanase-2 (or ADAMTS5), expression [19]. [score:11]
Rasheed Z. Rasheed N. Al-Shaya O. Epigallocatechin-3-O-gallate modulates global microRNA expression in interleukin-1β-stimulated human osteoarthritis chondrocytes: Potential role of EGCG on negative co-regulation of microRNA-140-3p and ADAMTS5Eur. [score:4]
[1 to 20 of 2 sentences]
49
[+] score: 14
In terms of cartilage, miR-140 targets histone deacetylase (HDAC) 4, which controls chondrocyte hypertrophy during skeletogenesis (Tuddenham et al., 2006) and controls cartilage homeostasis by regulating ADAMTS-5 and MMP-13 to protect against cartilage damage (Miyaki & Asahara, 2012). [score:4]
Deletion of miR-140 predisposed mice to develop age-related OA-like changes and further increased cartilage destruction in an OA animal mo del by directly targeting A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), aspartyl aminopeptidase (Dnpep), and insulin-like growth factor binding protein 5 (IGFBP-5). [score:4]
More recently, miR-140 was shown to directly mediate matrix metalloprotease (MMP)-13 expression in vitro (Tardif et al., 2009). [score:4]
For example, the major miRNA, miR-140, has been shown to function in chondrogenesis and cartilage development. [score:2]
[1 to 20 of 4 sentences]
50
[+] score: 14
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-27b, hsa-mir-122, hsa-mir-125b-1, hsa-mir-125b-2, hsa-mir-136, hsa-mir-146a, hsa-mir-150, hsa-mir-206, hsa-mir-155, hsa-mir-181b-2, hsa-mir-106b, hsa-mir-302a, hsa-mir-34b, hsa-mir-34c, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-367, gga-let-7i, gga-let-7a-3, gga-let-7b, gga-let-7c, gga-mir-125b-2, gga-mir-155, gga-mir-222a, gga-mir-221, gga-mir-92-1, gga-mir-19b, gga-mir-20a, gga-mir-19a, gga-mir-18a, gga-mir-17, gga-mir-16-1, gga-mir-15a, gga-mir-1a-2, gga-mir-206, gga-mir-223, gga-mir-106, gga-mir-302a, gga-mir-181a-1, gga-mir-181b-1, gga-mir-16-2, gga-mir-15b, gga-mir-140, gga-let-7g, gga-let-7d, gga-let-7f, gga-let-7a-1, gga-mir-146a, gga-mir-181b-2, gga-mir-181a-2, gga-mir-1a-1, gga-mir-1b, gga-let-7a-2, gga-mir-34b, gga-mir-34c, gga-let-7j, gga-let-7k, gga-mir-23b, gga-mir-27b, gga-mir-24, gga-mir-122-1, gga-mir-122-2, hsa-mir-429, hsa-mir-449a, hsa-mir-146b, hsa-mir-507, hsa-mir-455, hsa-mir-92b, hsa-mir-449b, gga-mir-146b, gga-mir-302b, gga-mir-302c, gga-mir-302d, gga-mir-455, gga-mir-367, gga-mir-429, gga-mir-449a, hsa-mir-449c, gga-mir-21, gga-mir-1458, gga-mir-1576, gga-mir-1612, gga-mir-1636, gga-mir-449c, gga-mir-1711, gga-mir-1729, gga-mir-1798, gga-mir-122b, gga-mir-1811, gga-mir-146c, gga-mir-15c, gga-mir-449b, gga-mir-222b, gga-mir-92-2, gga-mir-125b-1, gga-mir-449d, gga-let-7l-1, gga-let-7l-2, gga-mir-122b-1, gga-mir-122b-2
MiR-1a, miR-140 and miR-449 were significantly up-regulated in both tissues, while miR-455, miR-34b and miR-34c were only up-regulated with AIV infection in tracheae. [score:7]
Of particular interest, miR-1a, miR-140, and miR-449, which were highly expressed in infected tracheas than the non-infected ones, and also were differentially expressed between infected tissues (higher expression levels in infected tracheae than infected lungs). [score:7]
[1 to 20 of 2 sentences]
51
[+] score: 14
For example, miR-140 is a suppressor of p38 MAPK signal transduction pathway, and overexpression of this microRNA can reduce MEF2C expression [70]. [score:7]
miR-140 is a suppressor of p38 MAPK signaling and its overexpression can decrease MEF2C expression in a p38MAPK -dependent pathway. [score:7]
[1 to 20 of 2 sentences]
52
[+] score: 14
Moreover, the expression of lncRNA MEG3 was shown to be upregulated by pioglitazone to protect endothelial progenitor cells via decreasing miR-140-5p levels and increasing Hdac7 expression in subjects with metabolic syndrome [113]. [score:8]
Interestingly, miR-140 has been shown to physically interact in the nucleus with NEAT1, leading to increased NEAT1 expression and promotion of adipogenesis [107]. [score:3]
Li Z. Jin C. Chen S. Zheng Y. Huang Y. Jia L. Ge W. Zhou Y. Long non-coding RNA MEG3 inhibits adipogenesis and promotes osteogenesis of human adipose-derived mesenchymal stem cells via miR-140-5pMol. [score:3]
[1 to 20 of 3 sentences]
53
[+] score: 14
Our results, together with recent reports that miR-9, miR-132, and miR-140-5p regulate Foxp2/ FoxP2 expression (Foxp2 and FoxP2 denote respective rodent and avian genes) in animal mo dels [21, 22], highlight the importance of the FOXP2 3′ UTR sequence and the roles for miRNAs in regulating FOXP2 expression. [score:7]
We selected 12 miRNAs: miR-9, miR-19b, miR-27b, miR-92a, miR-140-5p, miR-190, miR-200a, let-7a, miR-129-5p, miR-582-5p, miR-892a, and miR-1237 (Figure  1) and tested whether they downregulate FOXP2 expression in cell culture systems. [score:6]
We found that miR-9, miR-19b, miR-140-5p, miR-200a, let-7a, miR-129-5p, miR-582-5p, and miR-892a reduced FOXP2 protein levels significantly (Figure  2A). [score:1]
[1 to 20 of 3 sentences]
54
[+] score: 14
Hand-2 deficient (−/−) gene led to implantation failure in mice (Okada et al. 2014) miR-140-3p Mature-microRNA Inhibited −2.236 3.73E-02 AASS, BCAS2, ERAP, NSF, WDR33miR-140-3p affect expression of putative targets in endometrial stromal cells in vitro (Okada et al. 2014) Embryonic implantation in humans depends on the interaction of the embryo with the receptive endometrium. [score:7]
Hand-2 deficient (−/−) gene led to implantation failure in mice (Okada et al. 2014) miR-140-3p Mature-microRNA Inhibited −2.236 3.73E-02 AASS, BCAS2, ERAP, NSF, WDR33miR-140-3p affect expression of putative targets in endometrial stromal cells in vitro (Okada et al. 2014) To clarify whether treatments of human endometrium with different estrogen concentrations affected embryo implantation, we used in vitro attachment mo del of human choriocarcinoma JAr cell spheroids to receptive-phase endometrial epithelial cell monolayers and Ishikawa cell monolayers (Fig. 1A, B, C, D, E and F). [score:7]
[1 to 20 of 2 sentences]
55
[+] score: 13
Five of the twenty snoRNA-like miRNAs, mir-664, mir-151, mir-605, mir-215 and mir-140 were selected for this analysis because they are expressed in HeLa cells. [score:3]
Indeed, mir-151 has been shown to be processed into its mature form by usual miRNA processing machinery [42] while functional targets of mir-140 have been experimentally validated [43]. [score:3]
Ten of the miRNAs in Table 2 have been identified with at least 10 reads and four of these (miR-151, miR-885, miR-140 and miR-520a) also have corresponding star reads of lower abundance. [score:1]
Only two (mir-215 and mir-140) of our twenty miRNAs encoded in predicted snoRNAs are classified as protypical in this study. [score:1]
We tested the predictions by experimentally showing that the precursors of five of the predicted snoRNA-like miRNAs, mir-664, mir-151, mir-605, mir-215 and mir-140, interact with dyskerin, a protein component of functional H/ACA snoRNPs. [score:1]
C RT-PCR used to detect co-precipitated hsa-mir-664, hsa-mir-151, hsa-mir-605, has-mir-215 and has-mir-140 miRNA precursors, with E2 box H/ACA snoRNA as positive control and hsa-pri-let-7g miRNA, U3 box C/D snoRNA, U1 snRNA, 5S rRNA and GAPDH pre-mRNA as negative controls for dyskerin -associated RNAs. [score:1]
Of the five extended miRNA regions that we experimentally found to be bound by dyskerin, three (mir-151, mir-140 and mir-215) have been further characterized and functionally validated, either by studies of their processing into their mature form or validation of their targets and effects. [score:1]
U1656 ACA56 mir-140 N/A 44.15 44.15>40000 [58] 10 [58] LSU. [score:1]
Indeed, the H/ACA snoRNAs predicted in the extended region around mir-549, mir-140, mir-1262 and mir-605 are all predicted to serve as guides for experimentally validated pseudouridylation sites whose guides are unknown, making these interesting candidates for further studies. [score:1]
[1 to 20 of 9 sentences]
56
[+] score: 13
Seven miRNAs had different expression levels between active TB and healthy controls: six miRNAs (hsa-miR-16, hsa-miR-137, hsa-miR-140-3p, hsa-miR-193a-3p, hsa-miR-501-5p, and hsa-miR-598) were upregulated while hsa-miR-95 was down-regulated. [score:9]
Both miR-150 and miR-140-3p were differentially expressed in macrophages infected in vitro and those from active TB patients. [score:3]
Of these, 13 miRNAs (hsa-let-7e, hsa-let-7f, hsa-miR-10a, hsa-miR-21, hsa-miR-26a, hsa-miR-99a, hsa-miR-140-3p, hsa-miR-150, hsa-miR-181a, hsa-miR-320, hsa-miR-339-5p, hsa-miR-425, and hsa-miR-582-5p) were repressed in the Beijing/W TB infected group (Fig 1). [score:1]
[1 to 20 of 3 sentences]
57
[+] score: 13
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-20a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-27a, hsa-mir-92a-1, hsa-mir-92a-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-15b, mmu-mir-23b, mmu-mir-27b, mmu-mir-130a, mmu-mir-133a-1, mmu-mir-140, mmu-mir-24-1, hsa-mir-196a-1, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, mmu-mir-206, hsa-mir-30c-2, hsa-mir-196a-2, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-200b, mmu-mir-301a, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-23b, hsa-mir-27b, hsa-mir-130a, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-206, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-196a-1, mmu-mir-196a-2, mmu-mir-200a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-18a, mmu-mir-20a, mmu-mir-24-2, mmu-mir-27a, mmu-mir-92a-2, hsa-mir-200c, hsa-mir-1-1, mmu-mir-1a-2, mmu-mir-17, mmu-mir-19a, mmu-mir-200c, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-19b-1, mmu-mir-92a-1, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-301a, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, hsa-mir-196b, mmu-mir-196b, dre-mir-196a-1, dre-mir-199-1, dre-mir-199-2, dre-mir-199-3, hsa-mir-18b, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-1-2, dre-mir-1-1, dre-mir-15a-1, dre-mir-15a-2, dre-mir-15b, dre-mir-17a-1, dre-mir-17a-2, dre-mir-18a, dre-mir-18b, dre-mir-18c, dre-mir-19a, dre-mir-20a, dre-mir-23b, dre-mir-24-4, dre-mir-24-2, dre-mir-24-3, dre-mir-24-1, dre-mir-27a, dre-mir-27b, dre-mir-27c, dre-mir-27d, dre-mir-27e, dre-mir-30c, dre-mir-92a-1, dre-mir-92a-2, dre-mir-92b, dre-mir-130a, dre-mir-133a-2, dre-mir-133a-1, dre-mir-133b, dre-mir-133c, dre-mir-140, dre-mir-196a-2, dre-mir-196b, dre-mir-200a, dre-mir-200b, dre-mir-200c, dre-mir-206-1, dre-mir-206-2, dre-mir-301a, dre-let-7j, hsa-mir-92b, mmu-mir-666, mmu-mir-18b, mmu-mir-92b, mmu-mir-1b, dre-mir-196c, dre-mir-196d, mmu-mir-3074-1, mmu-mir-3074-2, hsa-mir-3074, mmu-mir-133c, mmu-let-7j, mmu-let-7k, dre-mir-24b
Expression of mir23b and mir133b is conserved in zebrafish facial structuresBased on analysis of mir140 action, miRNA function during facial development is also present in zebrafish embryos. [score:4]
A SNP in the human MIR140 gene leads to reduced Mir140 expression in murine palatal mesenchymal cells (Li et al., 2011). [score:3]
One of the first examples of miRNA action in facial development is mir140, whose regulation of pdgfra is required for NCCs to migrate past the optic stalk on their way from the hindbrain to the future palate (Eberhart et al., 2008). [score:3]
Based on analysis of mir140 action, miRNA function during facial development is also present in zebrafish embryos. [score:2]
Single nucleotide polymorphism associated with nonsyndromic cleft palate influences the processing of miR-140. [score:1]
[1 to 20 of 5 sentences]
58
[+] score: 13
Compared to normal tissue with an expression profile normalized to 1, in tumor samples of the 14 CRC patients we observed a significant up-regulation for 3 miRNAs (miR-31, miR-21 and miR-708), and under expression in 7 others (miR-145, miR-139-5p, miR-486-5p, miR-378, miR-140-3p, miR-143 and miR-30c) (Table 3). [score:7]
For CRC, different degrees of correlation were found for the 24 miRNAs exhibiting altered expression: miR-106a was not correlated at all, while miR-195 exhibited the largest number of ties and was taken as a root node with 9 edges (degree 15.86); 8 links were detected for miR-28-3p (degree 15.66), and 7 links for miR-1280 (degree 13.79), miR-1246 (degree 13.05), and miR-140-3p (degree 12.12) (Figure 5, panel A). [score:3]
By miRNA-network analysis, tissue-specific patterns of miRNA deregulation were traced: the driving miRNAs were miR-195, miR-1280, miR-140-3p and miR-1246 in colorectal tumors, and miR-103, miR-23a and miR-15b in pancreatic cancers. [score:2]
The lowest scores were observed for miR-1280, miR-195 and miR-140-3p which were the vertices of complete graph (Figures 5, panel A and Table S4). [score:1]
[1 to 20 of 4 sentences]
59
[+] score: 12
In SC fat, expression of miR-27a, miR-30e, miR-140, miR-155, miR-210 was significantly higher and expression of miR-147 and miR-197 was lower in NGT as compared to the T2D group 10.1371/journal. [score:4]
Our data suggest that expression of miR-17-5p, miR-132, miR-134, miR-181a, miR-27a, miR-30e, miR-140, miR-147, miR-155, miR-197, and miR-210 play a role in the link between adipose tissue dysfunction and the development of obesity associated disorders including type 2 diabetes. [score:4]
In SC fat, expression of miR-27a, miR-30e, miR-140, miR-155, miR-210 was significantly higher and expression of miR-147 and miR-197 was lower in NGT as compared to the T2D group 10.1371/journal. [score:4]
[1 to 20 of 3 sentences]
60
[+] score: 12
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-96, hsa-mir-99a, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-192, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-139, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-210, hsa-mir-181a-1, hsa-mir-214, hsa-mir-215, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-134, hsa-mir-136, hsa-mir-146a, hsa-mir-150, hsa-mir-185, hsa-mir-190a, hsa-mir-194-1, hsa-mir-195, hsa-mir-206, hsa-mir-200c, hsa-mir-155, hsa-mir-181b-2, hsa-mir-128-2, hsa-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-99b, hsa-mir-296, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-370, hsa-mir-373, hsa-mir-374a, hsa-mir-375, hsa-mir-376a-1, hsa-mir-151a, hsa-mir-148b, hsa-mir-331, hsa-mir-338, hsa-mir-335, hsa-mir-423, hsa-mir-18b, hsa-mir-20b, hsa-mir-429, hsa-mir-491, hsa-mir-146b, hsa-mir-193b, hsa-mir-181d, hsa-mir-517a, hsa-mir-500a, hsa-mir-376a-2, hsa-mir-92b, hsa-mir-33b, hsa-mir-637, hsa-mir-151b, hsa-mir-298, hsa-mir-190b, hsa-mir-374b, hsa-mir-500b, hsa-mir-374c, hsa-mir-219b, hsa-mir-203b
MicroRNA-22 and microRNA-140 suppress NF-κB activity by regulating the expression of NF-κB coactivators. [score:6]
Izzotti et al. (2009a, b) have monitored the expression of 484 miRNAs in the lungs of mice exposed to cigarette smoking, the most remarkably downregulated miRNAs belonged to several miRNA families, such as let-7, miR-10, miR-26, miR-30, miR-34, miR-99, miR-122, miR-123, miR-124, miR-125, miR-140, miR-145, miR-146, miR-191, miR-192, miR-219, miR-222, and miR-223. [score:6]
[1 to 20 of 2 sentences]
61
[+] score: 11
Of these five targets, four miRNAs (miR-101, miR-140-5p, miR-448 and miR-485-5p) were downregulated in T-ALL patient specimens and T-ALL cell lines [55]. [score:6]
By performing computational target prediction, luciferase reporter system, and mutagenesis assays; five candidate miRNAs (miR-101, miR-520d-5p, miR-140-5p, miR-448 and miR-485-5p) were found to directly target TAL1. [score:5]
[1 to 20 of 2 sentences]
62
[+] score: 11
In a study, Shi and his colleagues provided evidence that miR-9 and miR-140-5p downregulate FOXP2 expression by targeting FOXP2 3’-UTR [140]. [score:8]
Interestingly, substantial miRNAs (miR-9, miR-132, let-7a and miR-140-5p) are found to be lost in the striatum of mammals which is a region important for speech and language, where FOXP2 is expressed [142, 143]. [score:3]
[1 to 20 of 2 sentences]
63
[+] score: 11
The studies revealed that miR-140 overexpression led to chemoresistance to various chemotherapeutics such as methotrexate (MTX) and 5- fluorouracil (5-FU). [score:3]
The cartilage specific microRNA-140 targets histone deacetylase 4 in mouse cells. [score:3]
Also, miR-140 negatively regulated histone deacetylase 4 (HDAC 4) resulting in 5-FU resistance. [score:2]
Some of the first known miRNAs that have been associated with drug sensitivity are miR-140 and miR-215 (Song et al., 2009, 2010; Zhu et al., 2012). [score:1]
Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells. [score:1]
Molecular mechanisms of the cartilage-specific microRNA-140 in osteoarthritis. [score:1]
[1 to 20 of 6 sentences]
64
[+] score: 11
Similar results were observed in p53 [+/+] and p53 [−/−] cells (Figure 2c): the expression levels of miR-3151 and miR-663b were upregulated in p53 [−/−] cells, while the expression levels of miR-140, miR-30b, miR-506, miR-124 and miR-30c were downregulated in p53 [−/−] cells compared with that in p53 [+/+] cells. [score:10]
Several miRNAs were proposed, among which seven of them were reported to be related to p53: miR-140, miR-30b, miR-3151, miR-506, miR-124, miR-30c, and miR-663b 19, 20, 21, 22, 23, 24 (Figure 2a). [score:1]
[1 to 20 of 2 sentences]
65
[+] score: 10
For example, MMP16, predicted target of miRs miR-27, miR-30 and miR-140, is an important protein regulating bone homeostasis through regulating osteocyte differentiation [58]. [score:5]
Among the miR expression of which was differentially expressed in the osteogenic tissues from adult and old donors, miRs with known function in bone biology were validated: let-7 [52], miR-21 [53], miR-30 [54], miR-96 [55], miR-27 [56], and miR-140 [57]. [score:5]
[1 to 20 of 2 sentences]
66
[+] score: 10
Control versus curcuminControl versus H [2]O [2]Control versus H [2]O [2]+curcumin Downregulated Downregulated DownregulatedmiRNA (miR)P valueFR (FC)miRNA (miR)P valueFR (FC)miRNA (miR)P valueFR (FC)miR-302c0.033−4.26 (0.24)miR-15a0.041−13.98 (0.07)miR-70.011−4.18 (0.24)miR-30e0.016−7.37 (0.14)let-7a0.031−5.91 (0.17)miR-30d0.014−3.40 (0.29)miR-30d0.019−4.19 (0.24)miR-1260.045−19.01 (0.05)miR-140–5p0.017−10.42 (0.10)miR-30b0.02−3.97 (0.30)miR-27a0.024−22. [score:10]
[1 to 20 of 1 sentences]
67
[+] score: 10
Previous studies reported that miR-140 [15], miR-145 [17], miR-195 [16] and miR-9500 [2] are downregulated in NSCLC-related biospecimens. [score:4]
In particular, miR-140 [15] and miR-195 [16] decrease tumour growth and metastasis through proliferative delay or arrest by targeting IGF-1R in NSCLC. [score:3]
In particular, miR-122 [12], miR-139 [13] and miR-140 [15] targeting to IGF-1R gene play important key roles during tumourigenesis or metastatic spread in an in vivo mo del of various malignant cells. [score:3]
[1 to 20 of 3 sentences]
68
[+] score: 10
The maximum number of predicted targets was 25 for miR-30d, and the minimum number of predicted targets was one for miR-1, miR-100 and rno-miR-140 (Table 1). [score:5]
These mRNAs are all included in the list of predicted target in Table 2. It was interesting to see that the four remaining miRNAs (miR-100, rno-miR-140, miR15a and miR-26a) were grouped in this network by IPA and not connected through the above cancer-related target mRNAs by the pathway designer and hence two of them (miR-100 and miR-15a) were not included in Figure 4A. [score:5]
[1 to 20 of 2 sentences]
69
[+] score: 10
Other miRNAs from this paper: hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-98, hsa-mir-99a, hsa-mir-100, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-196a-1, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-196a-2, hsa-mir-199a-2, hsa-mir-210, hsa-mir-181a-1, hsa-mir-214, hsa-mir-222, hsa-mir-223, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-146a, hsa-mir-150, hsa-mir-186, hsa-mir-188, hsa-mir-195, hsa-mir-200c, hsa-mir-155, hsa-mir-181b-2, hsa-mir-106b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-363, hsa-mir-302c, hsa-mir-370, hsa-mir-373, hsa-mir-374a, hsa-mir-328, hsa-mir-342, hsa-mir-326, hsa-mir-135b, hsa-mir-338, hsa-mir-335, hsa-mir-345, hsa-mir-424, hsa-mir-20b, hsa-mir-146b, hsa-mir-520a, hsa-mir-518a-1, hsa-mir-518a-2, hsa-mir-500a, hsa-mir-513a-1, hsa-mir-513a-2, hsa-mir-92b, hsa-mir-574, hsa-mir-614, hsa-mir-617, hsa-mir-630, hsa-mir-654, hsa-mir-374b, hsa-mir-301b, hsa-mir-1204, hsa-mir-513b, hsa-mir-513c, hsa-mir-500b, hsa-mir-374c
Comparison of miRNA expression of microdissected HRS cells from cHL patients to CD77+ GC B cells showed three downregulated miRNAs, namely, miR-520a, miR- 200a, and miR-614 and twelve upregulated miRNAs, namely, miR-20a, miR-21, miR-9, miR-155, miR-16, miR-140, miR-18a, miR-30b, miR-30a- 5p, miR-196a, miR-374, and miR-186 [36]. [score:9]
Distinctive miRNA signatures obtained using unsupervised hierarchical clustering could distinguish these three groups based on just 16 miRNAs with miR-17~92 cluster members (miR-17-5p, miR-17-3p, miR-18a, miR-19a, miR-20a, miR-20b, and miR-92) and its paralog miR-106a, being the predominant one in addition to miR-29a/c,miR-100, miR-199a*, miR-140, miR-630, and miR-16 [49]. [score:1]
[1 to 20 of 2 sentences]
70
[+] score: 9
Another down-regulated miRNA, miR-140, also suppresses the TGFβ pathway via repression of Smad3 in the murine multipotential mesenchymal cells [41]. [score:6]
The results (Fig. 1b ) confirmed that the expression patterns of miR-20a, miR-34a, miR-140 and miR-16 were consistent with those obtained after pre-PCR amplification. [score:3]
[1 to 20 of 2 sentences]
71
[+] score: 9
Finally, we found that this stem-like subpopulation could be targeted for differentiation with histone deacetylase (HDAC) inhibitors and DNA methyltransferase (DNMT) inhibitors, resulting in activation of tumor suppressor miR-140 [5]. [score:9]
[1 to 20 of 1 sentences]
72
[+] score: 9
The differential expression of eca-miR-140-3p is considered to be of low confidence, since the signal was mainly driven by just one sample and the differential expression was not significant after the exclusion of the outlier individual (Figure A4). [score:4]
After the exclusion of that outlier, eca-miR-140-3p did not show significant differential expression anymore (last plot; adjusted p = 0.106). [score:3]
Using DESeq2, we identified 11 miRNAs as statistically significant DEmiRs after accounting for the level of hemolysis: eca-miR-128, eca-miR-744, eca-miR-197, eca-miR-103 and the closely related eca-miR-107a, eca-miR-30d, eca-miR-140-3p, eca-miR-7, eca-miR-361-3p, eca-miR-148b-3p and eca-miR-215. [score:1]
The first plot indicates the borderline significant eca-miR-215 followed by the boxplot for eca-miR-140-3p which clearly indicates that the signal for that miRNA is predominantly driven by one extreme outlier individual. [score:1]
[1 to 20 of 4 sentences]
73
[+] score: 9
Regarding the number of target mRNAs; miR-944, miR-141-3p, and miR-203a ranked top three among down-regulated miRNAs, while miR-140-3p, miR-452-5p, and miR-137 located top three of up-regulated miRNAs (Figure 1). [score:9]
[1 to 20 of 1 sentences]
74
[+] score: 9
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-21, hsa-mir-22, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-30a, hsa-mir-31, hsa-mir-98, hsa-mir-99a, hsa-mir-101-1, hsa-mir-16-2, hsa-mir-192, hsa-mir-197, hsa-mir-199a-1, hsa-mir-208a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-187, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-211, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-138-2, hsa-mir-142, hsa-mir-143, hsa-mir-144, hsa-mir-145, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-138-1, hsa-mir-146a, hsa-mir-200c, hsa-mir-155, hsa-mir-128-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-99b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-375, hsa-mir-328, hsa-mir-337, hsa-mir-338, hsa-mir-339, hsa-mir-384, hsa-mir-424, hsa-mir-429, hsa-mir-449a, hsa-mir-485, hsa-mir-146b, hsa-mir-494, hsa-mir-497, hsa-mir-498, hsa-mir-520a, hsa-mir-518f, hsa-mir-499a, hsa-mir-509-1, hsa-mir-574, hsa-mir-582, hsa-mir-606, hsa-mir-629, hsa-mir-449b, hsa-mir-449c, hsa-mir-509-2, hsa-mir-874, hsa-mir-744, hsa-mir-208b, hsa-mir-509-3, hsa-mir-1246, hsa-mir-1248, hsa-mir-219b, hsa-mir-203b, hsa-mir-499b
Targets of the most remarkably down-regulated miRNAs (let-7, miR-10, miR-26, miR-30, miR-34, miR-99, miR-122, miR-123, miR-124, miR-125, miR-140, miR-145, miR-146, miR-191, miR-192, miR-219, miR-222, and miR-223) regulate proliferation, gene expression, stress response, apoptosis, and angiogenesis. [score:9]
[1 to 20 of 1 sentences]
75
[+] score: 9
Thus, miR-140-5p (p < 0.0001) targets HDAC4 as well as HDAC7, both histone class II deacetylases which regulate transcription and are well established circadian regulators [54]. [score:5]
Another epigenetic clock regulator, DNMT1, is also a miR-140-5p target [1]. [score:4]
[1 to 20 of 2 sentences]
76
[+] score: 9
The expressions of 17 of the dysregulated miRNAs (miR-145*, -145, -214, -4770, -378*, -99a, -193b, -100, -125b, -3195, -30e*, -9, -125a-5p, let-7b, miR-24-1*, -1979, and -768-3p) were significantly lower in both colon and rectal cancers compared with normal tissues, but of the remaining 5, miR-133a and miR-140-3p were found significantly downregulated (P<0.05) only in rectal cancers, and miR-27b*, miR-30a, and miR-29b-2* were significantly downregulated only in colon cancers (P<0.05; Figure 1). [score:9]
[1 to 20 of 1 sentences]
77
[+] score: 9
Other miRNAs from this paper: hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-27a, hsa-mir-30a, hsa-mir-32, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-107, hsa-mir-129-1, hsa-mir-30c-2, hsa-mir-139, hsa-mir-181c, hsa-mir-204, hsa-mir-212, hsa-mir-181a-1, hsa-mir-222, hsa-mir-15b, hsa-mir-23b, hsa-mir-132, hsa-mir-138-2, hsa-mir-142, hsa-mir-129-2, hsa-mir-138-1, hsa-mir-146a, hsa-mir-154, hsa-mir-186, rno-mir-324, rno-mir-140, rno-mir-129-2, rno-mir-20a, rno-mir-7a-1, rno-mir-101b, hsa-mir-29c, hsa-mir-296, hsa-mir-30e, hsa-mir-374a, hsa-mir-380, hsa-mir-381, hsa-mir-324, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-15b, rno-mir-17-1, rno-mir-18a, rno-mir-19b-1, rno-mir-19b-2, rno-mir-19a, rno-mir-21, rno-mir-23a, rno-mir-23b, rno-mir-24-1, rno-mir-24-2, rno-mir-27a, rno-mir-29c-1, rno-mir-30e, rno-mir-30a, rno-mir-30c-2, rno-mir-32, rno-mir-92a-1, rno-mir-92a-2, rno-mir-93, rno-mir-107, rno-mir-129-1, rno-mir-132, rno-mir-138-2, rno-mir-138-1, rno-mir-139, rno-mir-142, rno-mir-146a, rno-mir-154, rno-mir-181c, rno-mir-186, rno-mir-204, rno-mir-212, rno-mir-181a-1, rno-mir-222, rno-mir-296, rno-mir-300, hsa-mir-20b, hsa-mir-431, rno-mir-431, hsa-mir-433, rno-mir-433, hsa-mir-410, hsa-mir-494, hsa-mir-181d, hsa-mir-500a, hsa-mir-505, rno-mir-494, rno-mir-381, rno-mir-409a, rno-mir-374, rno-mir-20b, hsa-mir-551b, hsa-mir-598, hsa-mir-652, hsa-mir-655, rno-mir-505, hsa-mir-300, hsa-mir-874, hsa-mir-374b, rno-mir-466b-1, rno-mir-466b-2, rno-mir-466c, rno-mir-874, rno-mir-17-2, rno-mir-181d, rno-mir-380, rno-mir-410, rno-mir-500, rno-mir-598-1, rno-mir-674, rno-mir-652, rno-mir-551b, hsa-mir-3065, rno-mir-344b-2, rno-mir-3564, rno-mir-3065, rno-mir-1188, rno-mir-3584-1, rno-mir-344b-1, hsa-mir-500b, hsa-mir-374c, rno-mir-29c-2, rno-mir-3584-2, rno-mir-598-2, rno-mir-344b-3, rno-mir-466b-3, rno-mir-466b-4
Finally, other subsets of miRNAs were either up-regulated (miR-23a-3p, miR132-3p, miR-146a-5p, miR-154-3p, miR-181d-5p, miR-212-3p, miR-212-5p, miR-344b-5p, miR-380-3p, miR-410-3p, miR-433-3p and miR-3584; Fig. 2, Supplementary Fig. S4), or down-regulated (miR-29c-5p, miR-30a-5p, miR-30c-2-3p, miR-30e-3p, miR-138-5p, miR-140-3p, miR-551b-3p and miR-652-3p; Fig. 2, Supplementary Fig. S5) during all phases of the disease. [score:9]
[1 to 20 of 1 sentences]
78
[+] score: 8
Similar to increased expression predicted by RNA-Seq analysis, we found a significant increase in the expression of MIR26A-2-3P (5.9 fold, p < 0.05), MIR126-5P (12.6 fold, p < 0.05), MIR140-5P (5.6 fold, p < 0.05), MIR29A-5P (6 fold, p < 0.05), MIR374A-3P (10.2 fold, p < 0.05) and MIR147B (3.6 fold, p < 0.05) by qPCR (Fig.   4B). [score:5]
We used qPCR to confirm expression patterns predicted by RNA-Seq analysis for 8 miRNA (MIR29A-5P, MIR140-5P, MIR126P, MIR374A-3P, MIR26A-2-3P and MIR147B, MIR941 and MIR589-5P) that were induced following treatment of any eCig liquid (ANY LIQUID). [score:3]
[1 to 20 of 2 sentences]
79
[+] score: 8
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-96, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-107, hsa-mir-16-2, hsa-mir-196a-1, hsa-mir-198, hsa-mir-129-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-196a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-204, hsa-mir-210, hsa-mir-211, hsa-mir-212, hsa-mir-181a-1, hsa-mir-214, hsa-mir-215, hsa-mir-216a, hsa-mir-217, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-23b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-137, hsa-mir-138-2, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-129-2, hsa-mir-138-1, hsa-mir-146a, hsa-mir-150, hsa-mir-184, hsa-mir-185, hsa-mir-195, hsa-mir-206, hsa-mir-320a, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-181b-2, hsa-mir-128-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-99b, hsa-mir-296, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-365a, hsa-mir-365b, hsa-mir-375, hsa-mir-376a-1, hsa-mir-378a, hsa-mir-382, hsa-mir-383, hsa-mir-151a, hsa-mir-148b, hsa-mir-338, hsa-mir-133b, hsa-mir-325, hsa-mir-196b, hsa-mir-424, hsa-mir-20b, hsa-mir-429, hsa-mir-451a, hsa-mir-409, hsa-mir-412, hsa-mir-376b, hsa-mir-483, hsa-mir-146b, hsa-mir-202, hsa-mir-181d, hsa-mir-499a, hsa-mir-376a-2, hsa-mir-92b, hsa-mir-33b, hsa-mir-151b, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-301b, hsa-mir-216b, hsa-mir-103b-1, hsa-mir-103b-2, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-378b, hsa-mir-320e, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-219b, hsa-mir-203b, hsa-mir-451b, hsa-mir-499b, hsa-mir-378j
Transcriptional factor sox9, for example, is essential for morphogenesis of condensation and cartilage differentiation in zebrafish (Yan et al. 2002) and regulates the expression of miR-140 (Nakamura et al. 2012). [score:4]
However, miR-140 acts independently of sox9 in the regulation of palatal skeleton development by modulating pdgf-receptor alpha, which is required for migration of palatal precursor and neural crest cells (Eberhart et al. 2008). [score:3]
Rakoczy et al. (2013) reported up to 2.6-fold increase in the number of Leydig cells in miR-140-3p ablated mice. [score:1]
[1 to 20 of 3 sentences]
80
[+] score: 8
For example, miR-144/451 inhibits cancer metastasis by targeting ADAMTS5 and ADAM10 in human epithelial cancers [36]; miR-122-5p reduces trastuzumab resistance by regulating ADAM10 in breast cancer [37]; miR-140-5p can repress tumor progression by targeting ADAM10 in human tongue and hypopharyngeal squamous cancer cells [38, 39]. [score:8]
[1 to 20 of 1 sentences]
81
[+] score: 8
Since E2 stimulation has been recently shown to enhance breast tumor-initiating cell survival (through downregulation of miR-140), which targets SOX2, this suggests a bidirectional cross-talk interaction to regulate breast cancer activity. [score:8]
[1 to 20 of 1 sentences]
82
[+] score: 8
From the 20 most differentially regulated microRNAs (10 most up-regulated and 10 most down-regulated, see Table 2) 7 are shared with female breast cancer (miR-21, miR-127, miR-122a, miR-135b, miR-140, miR-497, miR-145). [score:8]
[1 to 20 of 1 sentences]
83
[+] score: 8
Interestingly, miR-27a, miR-140 and miR-155, down-regulated in subcutaneous fat from DM-2 patients [26], were also down-regulated during adipocyte differentiation. [score:7]
21 hsa-miR-140-3p −1.22 hsa-miR-450a −1.23 hsa-miR-210 †† −1.24 1.48 hsa-miR-26b −1.25 hsa-miR-10b −1.25 −1.25 hsa-miR-101 −1.26 −1.28 hsa-let-7c −1.28 hsa-miR-98 −1.29 −1.21 hsa-miR-23a −1.30 hsa-miR-22* −1.34 −1.42 hsa-miR-337-3p −1.38 −1.23 hsa-miR-31 −1.39 −1.34 hsa-miR-365 −1.43 −1.38 hsa-miR-137 −1.46 −1.45 hsa-miR-494 −1.55 hsa-miR-29b −1.82 −1.93 hsa-miR-221 † −1.88 −1.84 hsa-miR-29c −2.33 hsa-let-7i 1.21 hsa-miR-125b † −1.24 hsa-miR-195 −1. [score:1]
[1 to 20 of 2 sentences]
84
[+] score: 7
It was concluded that in the cancerous tissues, i. e., miR-141, miR-200a, miR-200b, and miR-200c, had the highest level of up-regulation while miR-125b, miR-140, miR-145, and miR-199a were the most down-regulated. [score:7]
[1 to 20 of 1 sentences]
85
[+] score: 7
These mutations, which alter the sequence of a predicted target site for miR-140, were found to segregate with the disease phenotype and were not detected in a large set of human controls. [score:6]
These data strongly suggest the pathogenic role of the impaired miR-140- REEP1 binding in some SPG31 families, although so far no functional data have been provided to consolidate this hypothesis. [score:1]
[1 to 20 of 2 sentences]
86
[+] score: 7
miR-140-5p also displayed significant increase of expression in all three glioblastoma stem cell lines tested, although with much lower fold induction (Fig. 2C). [score:3]
0036248.g002 Figure 2The expression levels of miR-10a (A), miR-10b (B), miR-140-5p (C), miR-124 (D), and miR-874 (E) in three glioblastoma stem cell (GSC) lines were measured by real-time RT-PCR, and compared to their expression in three neural stem cell (NSC) lines. [score:2]
The expression levels of miR-10a (A), miR-10b (B), miR-140-5p (C), miR-124 (D), and miR-874 (E) in three glioblastoma stem cell (GSC) lines were measured by real-time RT-PCR, and compared to their expression in three neural stem cell (NSC) lines. [score:2]
[1 to 20 of 3 sentences]
87
[+] score: 7
miR-200a and miR-141 were identified as highly upregulated in cancer, whereas miR-199a, miR-140, miR-145, and miR-125b1 were most significantly downregulated. [score:7]
[1 to 20 of 1 sentences]
88
[+] score: 7
Inhibition of colorectal cancer stem cell survival and invasive potential by hsa-miR-140-5p mediated suppression of Smad2 and autophagy. [score:5]
Dicer (Iliou et al., 2014) and multiple miRNAs [including, miR-34a (Bu et al., 2013, 2016), miR-106b (Zheng et al., 2015a), miR-140 (Zhai et al., 2015), miR-146a (Hwang et al., 2014), miR-183 (Wellner et al., 2009), miR-200 (Wellner et al., 2009), miR-203 (Wellner et al., 2009), miR-215 (Jones et al., 2015), miR-302b (Zhu et al., 2012), miR-328 (Xu et al., 2012b), miR-363 (Tsuji et al., 2014), miR-371 (Li et al., 2015c) and miR-451 (Bitarte et al., 2011)] reportedly regulate CRC TICs. [score:2]
[1 to 20 of 2 sentences]
89
[+] score: 7
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-21, hsa-mir-22, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-99a, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-99a, mmu-mir-140, mmu-mir-10b, mmu-mir-181a-2, mmu-mir-24-1, mmu-mir-191, hsa-mir-192, hsa-mir-148a, hsa-mir-30d, mmu-mir-122, hsa-mir-10b, hsa-mir-181a-2, hsa-mir-181a-1, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-122, hsa-mir-191, hsa-mir-320a, mmu-mir-30d, mmu-mir-148a, mmu-mir-192, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-21a, mmu-mir-22, mmu-mir-24-2, mmu-mir-26a-1, mmu-mir-92a-2, mmu-mir-25, mmu-mir-181a-1, mmu-mir-26a-2, mmu-mir-92a-1, hsa-mir-26a-2, hsa-mir-423, hsa-mir-451a, mmu-mir-451a, hsa-mir-486-1, mmu-mir-486a, mmu-mir-423, bta-mir-26a-2, bta-let-7f-2, bta-mir-148a, bta-mir-21, bta-mir-30d, bta-mir-320a-2, bta-mir-99a, bta-mir-181a-2, bta-mir-27b, bta-mir-140, bta-mir-92a-2, bta-let-7d, bta-mir-191, bta-mir-192, bta-mir-22, bta-mir-423, bta-let-7g, bta-mir-10b, bta-mir-24-2, bta-let-7a-1, bta-let-7f-1, bta-mir-122, bta-let-7i, bta-mir-25, bta-let-7a-2, bta-let-7a-3, bta-let-7b, bta-let-7c, bta-let-7e, hsa-mir-1246, bta-mir-24-1, bta-mir-26a-1, bta-mir-451, bta-mir-486, bta-mir-92a-1, bta-mir-181a-1, bta-mir-320a-1, mmu-mir-486b, hsa-mir-451b, bta-mir-1246, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-mir-451b, mmu-let-7k, hsa-mir-486-2
There were eight microRNAs (bta-miR-27b, bta-miR-191, bta-miR-30d, bta-miR-451, bta-miR-25, bta-miR-140, bta-miR-24-3p, and bta-miR-122), that were upregulated in older animals in the present study, and upregulated in fetal muscle tissue of the study. [score:7]
[1 to 20 of 1 sentences]
90
[+] score: 7
Other miRNAs from this paper: hsa-let-7b, mmu-mir-140, mmu-mir-185, hsa-mir-185, mmu-let-7b
Sci Rep 2. 35 Takata A, Otsuka M, Yoshikawa T, Kishikawa T, Hikiba Y, et al (2013) MicroRNA-140 acts as a liver tumor suppressor by controlling NF-κB activity by directly targeting DNA methyltransferase 1 (Dnmt1) expression. [score:7]
[1 to 20 of 1 sentences]
91
[+] score: 7
Of 29 miRs, they showed that only 4 (miR-141, miR-200a, miR-200b, and miR-200c) were upregulated and 25 were downregulated, including miR-199a, miR-140, miR-145, and miR-125b-1 in the cancer samples [21]. [score:7]
[1 to 20 of 1 sentences]
92
[+] score: 6
Expression levels of fru-miR-196a-5p, fru-miR-206-3p, fru-miR-194-5p, fru-miR-192-5p, and fru-miR-10b-5p in slow muscle were 1305-, 529-, 93-, 85-, and 77-fold higher, respectively, compared with cardiac muscle, while expression levels of fru-miR-187-3p, fru-miR-30e-3p, fru-miR-140-3p, fru-miR-218a-5p, and fru-miR-140-5p were 16-, 16-, 10-, 8-, and 6-fold higher, respectively, in cardiac muscle compared with slow muscle. [score:3]
Fru-miR-206-3p, fru-miR-10b-5p, fru-miR-10d-5p, fru-miR-133b-3p, and fru-miR-133-3p exhibited 434, 77, 60, 17, and 15 times higher levels of expression, respectively, in fast muscle compared with cardiac muscle, while fru-miR-144-5p, fru-miR-499-5p, fru-miR-187-3p, fru-miR-499a-5p, and fru-miR-140-3p exhibited 51-, 41-, 37-, 33-, and 17-fold higher expression levels, respectively, in heart muscle compared with fast muscle. [score:3]
[1 to 20 of 2 sentences]
93
[+] score: 6
However, they only demonstrated that miR-140 -mediated NEAT1 expression is required for adipogenesis, without providing the underlying mechanism of how the increased NEAT1 contributed to adipogenesis. [score:3]
Mature miR-140 interacts with NEAT1 in the nucleus, and this subsequently increases NEAT1 expression leading to adipogenesis [80]. [score:3]
[1 to 20 of 2 sentences]
94
[+] score: 6
Two miRNAs were highly expressed in airway smooth muscle cells, miR-16 and miR-140. [score:3]
For example, miR-140 was predominantly expressed in airway smooth muscle cells. [score:3]
[1 to 20 of 2 sentences]
95
[+] score: 6
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-98, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-107, hsa-mir-16-2, hsa-mir-198, hsa-mir-148a, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-205, hsa-mir-210, hsa-mir-181a-1, hsa-mir-222, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-23b, hsa-mir-27b, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-132, hsa-mir-137, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-144, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-134, hsa-mir-136, hsa-mir-146a, hsa-mir-150, hsa-mir-184, hsa-mir-185, hsa-mir-186, hsa-mir-206, hsa-mir-320a, hsa-mir-200c, hsa-mir-128-2, hsa-mir-200a, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-299, hsa-mir-26a-2, hsa-mir-373, hsa-mir-376a-1, hsa-mir-342, hsa-mir-133b, hsa-mir-424, hsa-mir-429, hsa-mir-433, hsa-mir-451a, hsa-mir-146b, hsa-mir-494, hsa-mir-193b, hsa-mir-455, hsa-mir-376a-2, hsa-mir-33b, hsa-mir-644a, hsa-mir-548d-1, hsa-mir-548d-2, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-301b, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-320e, hsa-mir-3613, hsa-mir-4668, hsa-mir-4674, hsa-mir-6722
During the preclinical phase of prion disease, a cluster of genes and miRNAs are dysregulated, such as miRNA-132-3p, miRNA-124a-3p, miRNA-16-5p, miRNA-26a-5p, miRNa-29a-3p, and miRNA-140-5p, and they follow associated patterns of expression (Majer et al., 2012). [score:6]
[1 to 20 of 1 sentences]
96
[+] score: 6
Wang C Song X Li Y Han F Gao S Wang X Xie S Lv C Low-dose paclitaxel ameliorates pulmonary fibrosis by suppressing TGF-β1/Smad3 pathway via miR-140 upregulationPLoS One. [score:6]
[1 to 20 of 1 sentences]
97
[+] score: 6
By analysis of the genome-wide expression profiling of miRNAs, Yan and his colleagues showed that seven miRNAs of hsa-miR-497, hsa-miR-31, hsa-miR-355, hsa-miR-320, rno-mir-140, hsa-miR-127 and hsa-miR-30a-3p were significantly downregulated in BC [20]. [score:6]
[1 to 20 of 1 sentences]
98
[+] score: 6
Correspondingly, the highly expressed miRNAs in cancerous penile tissues were let-7f-5p, let-7a-5p, let-7b-5p, let-7c-5p, miR-140-3p, miR-199b-3p, let-7g-5p, miR-199a-3p, let-7e-5p and miR-143-3p possessed the top abundant expression levels. [score:5]
In normal penile tissues, let-7a-5p, let-7f-5p, let-7b-5p, let-7c-5p, miR-140-3p, let-7g-5p, let-7e-5p, miR-103a-3p, miR-320a, miR-143-3p were the top abundant miRNAs. [score:1]
[1 to 20 of 2 sentences]
99
[+] score: 6
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-17, hsa-mir-21, hsa-mir-29a, hsa-mir-96, mmu-let-7g, mmu-let-7i, mmu-mir-124-3, mmu-mir-140, mmu-mir-181a-2, mmu-mir-182, mmu-mir-183, mmu-mir-194-1, mmu-mir-200b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-181a-1, hsa-mir-200b, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-194-1, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-21a, mmu-mir-29a, mmu-mir-96, mmu-mir-34a, mmu-mir-135b, hsa-mir-200c, hsa-mir-181b-2, mmu-mir-17, mmu-mir-200c, mmu-mir-181a-1, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-181b-1, mmu-mir-181c, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-376c, hsa-mir-376a-1, mmu-mir-376a, hsa-mir-135b, mmu-mir-181b-2, mmu-mir-376b, dre-mir-34a, dre-mir-181b-1, dre-mir-181b-2, dre-mir-182, dre-mir-183, dre-mir-181a-1, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-15a-1, dre-mir-15a-2, dre-mir-17a-1, dre-mir-17a-2, dre-mir-21-1, dre-mir-21-2, dre-mir-29a, dre-mir-96, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-140, dre-mir-181c, dre-mir-194a, dre-mir-194b, dre-mir-200b, dre-mir-200c, hsa-mir-376b, hsa-mir-181d, hsa-mir-507, dre-let-7j, dre-mir-135b, dre-mir-181a-2, hsa-mir-376a-2, mmu-mir-376c, dre-mir-34b, dre-mir-34c, mmu-mir-181d, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-let-7k, dre-mir-181a-4, dre-mir-181a-3, dre-mir-181a-5, dre-mir-181b-3, dre-mir-181d, mmu-mir-124b
The expression data is based on in situ hybridization experiments of P0 mouse inner ear sections, except for miR-140 at P1, and miR-124a and -100a at P5 (Weston et al., 2006; Friedman et al., 2009; Wang et al., 2010a; Elkan-Miller et al., 2011; Yan et al., 2012). [score:3]
The expression data is based on in situ hybridization experiments of P0 mouse inner ear sections, except for miR-194 at E16.5, miR-140 at P1 and miR-124a and -100a at P5. [score:3]
[1 to 20 of 2 sentences]
100
[+] score: 6
Developmental expression profiling of the murine CNS revealed 12 miRNAs (miR-9, miR-17-5p, miR-124a, miR-125a, miR-125b, miR-130a, miR-140, miR-181a, miR-199a, miR-205, miR-214, miR-301) with significantly higher expression at embryonic versus postnatal time points. [score:6]
[1 to 20 of 1 sentences]