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188 publications mentioning hsa-mir-130a (showing top 100)

Open access articles that are associated with the species Homo sapiens and mention the gene name mir-130a. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 354
Other miRNAs from this paper: mmu-mir-130a
After correction for multiple testing, we identified 31 up-regulated and 13 down-regulated proteins in the 32Dcl3 miR-130a clone, and 19 up-regulated and 15 down-regulated proteins in Kasumi-1 cells, following miR-130a inhibition (q < 0.01). [score:15]
In the 32Dcl3 clone, putative targets were more up-regulated than the remaining quantified proteins following miR-130a inhibition, and three significantly derepressed proteins (NFYC, ISOC1, and CAT) are putative miR-130a targets with good RAIN scores. [score:10]
We also created a network including inferred, putative neutrophil miR-130a targets and identified the transcription factors Myb and CBF-β as putative miR-130a targets, which may regulate the primary granule proteins MPO and PRTN3 and other proteins differentially expressed following miR-130a inhibition in the 32Dcl3 clone. [score:10]
The significantly down-regulated Smarcb1 associates with Smarcd2, which is a predicted miR-130a target and down-regulated, although not significantly, in this study. [score:9]
We identified subsets of the murine and human neutrophil proteomes significantly regulated by miR-130a, which likely represent a mixture of direct targets, including NFYC, ISOC1, and CAT, and mainly indirect miR-130a targets. [score:8]
We found potential targets to be more up-regulated after miR-130a inhibition for the 32Dcl3 miR-130a clone (Kolmogorov–Smirnov test, p-value = 0.018) as demonstrated by the right shift of the curve showing higher M/H ratios. [score:8]
Linking these to putative miR-130a targets, we provide an association network of potential direct and indirect miR-130a targets that expands our knowledge on the role of miR-130a in neutrophil development and is a valuable platform for further experimental studies. [score:8]
CBF-β is up-regulated 1.35-fold (although not statistically significant) in the 32Dcl3 miR-130a clone following miR-130a inhibition and a candidate upstream regulator of three proteins within the regulated subset: MPO, IL-2Ra (Ingenuity Pathway analysis) and proteinase 3 (PRTN3, author observations, unpublished). [score:8]
If Myb is up-regulated following inhibition of miR-130a, this could lead to the observed increases of its targets, the primary granule proteins MPO [49] and PRTN3 [50] (Fig.   4). [score:8]
We demonstrated that substantial inhibition of miR-130a affects the overall expression of predicted target proteins in the murine neutrophil mo del system. [score:7]
These fold changes are included in the network to also indicate the observed direction of strongly predicted targets quantified but not significantly regulated within the data set In murine cells, RAIN does not identify Smad4 as a miR-130a target. [score:7]
Based on these analyses, we identified Myb and CBF-β as putative direct miR-130a targets and potential regulators of the primary granule proteins MPO and PRTN3 following miR-130a inhibition in the 32Dcl3 miR-130a clone. [score:7]
miR-130a is highly expressed during early neutrophil development and regulates target proteins important for this process. [score:7]
We showed that miR-130a suppresses expression of Smad4 and thereby reduces sensitivity to TGF-β1 -induced growth inhibition [9]. [score:7]
These fold changes are included in the network to also indicate the observed direction of strongly predicted targets quantified but not significantly regulated within the data setIn murine cells, RAIN does not identify Smad4 as a miR-130a target. [score:7]
RAIN does identify a weak interaction, although below the network cut-off, between Smad4 and NFYC, which is significantly up-regulated upon miR-130a inhibition. [score:6]
Of these three only MPO and PRTN3 were identified in the Kasumi-1 experiment, and only PRTN3 was borderline significantly up-regulated (q = 0.0113), probably reflecting the greater degree of miR-130a inhibition by anti-miR-130a-LNA observed in the 32Dcl3 miR-130a clone (Additional file 3: Figure S2). [score:6]
Three derepressed proteins (NFYC, ISOC1, and CAT) with miR-130a association probabilities within the top 20 % were found in the 32Dcl3 miR-130a clone and one (Phosphatidylinositide phosphatase SAC1, SACM1L) in Kasumi-1 cells (Fig.   2), indicating that most of the de-regulated proteins are either indirectly regulated by miR-130a or bona fide miR-130a targets not found by RAIN. [score:6]
Red: up-regulated >0.3 (log2 ratio) upon miR-130a inhibition. [score:6]
Fig. 4 RAIN networks of potential miR-130a targets (with miR-130a association probabilities in the top 20 %) and differentially regulated proteins identified for the 32Dcl3 miR-130a clone following miR-130a inhibition. [score:6]
Green: down-regulated < −0.3 (log2 ratio) upon miR-130a inhibition. [score:6]
Using pulsed stable isotope labelling of amino acids in cell culture and mass spectrometry for protein identification and quantitation, we found 44 and 34 proteins that were significantly regulated following inhibition of miR-130a in a miR-130a -overexpressing 32Dcl3 clone and Kasumi-1 cells, respectively. [score:6]
We identified important myeloid regulatory proteins, such as Myb and Core -binding factor beta (CBF-β), as putative direct miR-130a targets. [score:5]
We demonstrate that inhibition of miR-130a with an anti-miR-130a oligonucleotide in a miR-130a -overexpressing 32Dcl3 clone and in Kasumi-1 cells results in significant changes in the levels of 44 out of 2092 proteins and 34 out of 1238 proteins, respectively. [score:5]
TargetScan identifies Smad4 as a human miR-130a target with two seed matches (MREs) in the Smad4 3′ UTR. [score:5]
We found that putative miR-130a target proteins are more induced than the remaining proteins quantified in the 32Dcl3 miR-130a clone following miR-130a inhibition. [score:5]
The murine myeloblast-derived cell line 32Dcl3 was stably transfected with a miR-130a -expressing plasmid, resulting in a clone over -expressing miR-130a. [score:5]
Not much is known about ISOC1, also significantly derepressed by miR-130a inhibition and a highly predicted miR-130a target, other than that it associates with peroxisomes, has enzymatic activity, and may promote cell growth [53, 54]. [score:5]
This confirms that there is an overall greater effect of inhibiting miR-130a in cells from the 32Dcl3 miR-130a clone where the free miR-130a pool is much more reduced (~31 fold reduction) than in the Kasumi-1 cell line (~2.3 fold reduction) upon LNA -mediated inhibition (Additional file 3: Figure S2). [score:5]
The same MREs are also found in the murine Smad4 3′ UTR, but presumably other factors of the TargetScan algorithm prevent its prediction of murine Smad4 as a miR-130a target since murine and human miR-130a are identical. [score:5]
miR-130a also represses appropriate cell cycle exit and secondary granule protein expression by targeting C/EBPε in neutrophil precursors [9, 11]. [score:5]
The proteins identified in MS were compared with the top 20 % best scoring RAIN association probabilities for miR-130a to a) find potential miR-130a targets among the quantified proteins for the two cell lines, and to b) identify potential miR-130a target proteins for the miR-130a association network that might associate with proteins within the regulated protein subset found for the 32Dcl3 miR-130a clone. [score:5]
Finally, we constructed miR-130a target protein networks including the proteins identified in this study in order to find pathways affected by miR-130a in the context of neutrophil development. [score:4]
A Kolmogorov-Smirnov test of equality between distributions results in the following: p-value = 0.018 for the comparison between M/H ratios of proteins with good RAIN scores and the M/H ratios of proteins without scores; p-value = 0.042 for the M/H ratios of proteins with good RAIN scores and the M/H ratios of all remaining proteinsSecondly, we used RAIN to determine potential miR-130a targets within the subsets of significantly regulated proteins. [score:4]
First, we used RAIN to determine whether changes in protein levels could be directly attributed to the inhibition of miR-130a. [score:4]
This indicates that, in addition to transcription factors, miR-130a may target other types of transcriptional regulators as well as metabolic processes in neutrophil precursors. [score:4]
Together, these results provide significant insight into multiple miR-130a-regulated proteins and emphasize its important regulatory role in neutrophil development. [score:4]
A Kolmogorov-Smirnov test of equality between distributions results in the following: p-value = 0.018 for the comparison between M/H ratios of proteins with good RAIN scores and the M/H ratios of proteins without scores; p-value = 0.042 for the M/H ratios of proteins with good RAIN scores and the M/H ratios of all remaining proteins Secondly, we used RAIN to determine potential miR-130a targets within the subsets of significantly regulated proteins. [score:4]
dk/resources/rain/], to identify potential direct miR-130a targets among the proteins found within our two studies (see for details). [score:4]
We have previously experimentally identified Smad4 as a direct miR-130a target in murine cells [9]. [score:4]
This complex plays an important role in cell cycle progression [52] and may thus be regulated in neutrophil precursors by miR-130a targeting two of its subunits. [score:4]
CBF-β, Myb, and miR-130a are co-expressed in early myeloid precursors, suggesting that miR-130a may have a buffer effect on their protein levels ([48, 51] and unpublished data). [score:3]
In summary, these and other interactions identified here can form the basis for further experimental identification of miR-130a regulation in neutrophil development extending further than just single miR-130a–mRNA interactions. [score:3]
The level of miR-130a inhibition correlated with the impact on protein levels. [score:3]
miR-130a Neutrophils pSILAC Quantitative proteomics RAIN miRNA target network Neutrophils are the most abundant leukocytes in human blood. [score:3]
CBF-β is a highly predicted miR-130a target (top 20 %). [score:3]
Fig. 2The intensities in MS as a function of log2 fold changes in protein expression between the anti–miR-130a-LNA and scrambled-LNA conditions for the 32Dcl3 miR-130a clone (a) and the Kasumi-1 cells (b). [score:3]
To identify additional potential regulatory networks involving miR-130a, we constructed association networks for the subset of 44 regulated proteins found for the 32Dcl3 miR-130a clone. [score:3]
pSILAC approach for identification of myeloid miR-130a target proteins. [score:3]
The Kasumi-1 cell line is derived from an acute myeloid leukemia patient with t(8;21)(q22;q22) chromosomal translocation and has a 2.5-fold higher endogenous expression of miR-130a than the level found in primary myeloblasts and promyelocytes isolated from normal human bone marrow [9]. [score:3]
Therefore, it cannot be excluded that certain interesting miR-130a targets will be missed using RAIN due to this restriction in the underlying databases. [score:3]
NFYC is a predicted miR-130a target, but the effect of miR-130a might also be mediated by Smad4 or one of its other associated network proteins such as its heterotrimeric transcription factor complex partner NFYA. [score:3]
We used RAIN, a novel database for miRNA–protein and protein–protein interactions, to identify putative miR-130a targets. [score:3]
Fig. 3The cumulative distributions of M/H ratios of proteins with good RAIN scores (top 20 %, green), all remaining proteins (black), and proteins without RAIN scores (orange) as a function of log2 M/H fold changes in protein expression between the anti-miR-130a-LNA (M) and scrambled-LNA (H) conditions for the 32Dcl3 miR-130a clone. [score:3]
Three significantly induced proteins, nuclear transcription factor Y, gamma (NFYC), isochorismatase domain containing 1 (ISOC1), and catalase (CAT), are putative miR-130a targets with good scores in RAIN (RNA–protein Association and Interaction Networks) [http://rth. [score:3]
The murine myeloblast-derived cell line 32Dcl3 (ATCC® CRL-11346) was stably transfected with the expression plasmid pEGP-miR-130a (Cell Biolabs) as described previously [9]. [score:3]
Myb is a predicted miR-130a target but was not identified in either cell line. [score:3]
The last miR-130a target with a good RAIN score and significantly derepressed protein in the 32Dcl3 miR-130a clone is CAT. [score:3]
These two targets for miR-130a were suggested by in silico prediction algorithms based on conservation across species, sequence complementarity, and other miRNA–mRNA binding properties [12, 13]. [score:3]
We transiently transfected the 32Dcl3 miR-130a clone and Kasumi-1 cells with an inhibitory LNA probe against miR-130a (anti-miR-130a-LNA) or a scrambled-LNA (mock transfection). [score:3]
Identification of miR-130a targets in the neutrophil proteome. [score:3]
miR-130a expression in the 32Dcl3 and Kasumi-1 cell lines. [score:3]
Combining the significantly regulated murine protein subset with high-scoring putative miR-130a targets from the RAIN database in an interaction network, we identified subsets of proteins with potential roles in downstream miR-130a regulation relevant for further experimental investigation. [score:3]
The major miR-130a network includes the transcriptional activator Myb, which is more highly expressed in early neutrophil precursors compared to more mature cells [48]. [score:2]
We compared the fold changes of potential miR-130a target proteins with a good RAIN score (top 20 %) to those of proteins without scores (Fig.   3). [score:2]
A. H/M ratios of significantly regulated proteins in the 32Dcl3 miR-130a clone also identified and quantified for the Kasumi-1 cell line. [score:2]
Therefore, both CBF-β and Myb are potential direct miR-130a targets worth investigating further. [score:2]
miR-130a is highly expressed in early neutrophil precursors (myeloblasts and promyelocytes) compared to more mature precursors [9, 10]. [score:2]
Proteins differentially regulated by miR-130a were determined based on statistical significance rather than a fold change cut-off. [score:2]
We have experimentally identified miR-130a-regulated proteins within the neutrophil proteome. [score:2]
B. H/M ratios of significantly regulated proteins in the Kasumi-1 cell line also identified and quantified for the 32Dcl3 miR-130a clone. [score:2]
This resulted in a major miR-130a network as well as several minor, disconnected networks (Fig.   4). [score:1]
As most of the associations come from prediction algorithms, we chose the top 20 % highest scoring associations, which consist of 678 predictions, 5 experiments, and 6 text-mining interactions for miR-130a in mice. [score:1]
Proteins are represented by crosses (miR-130a association probability in top 20 %) or dots (miR-130a association probability below top 20 % or no score). [score:1]
Assignment of p-values to ratios (shown for the 32Dcl3 miR-130a clone). [score:1]
The sequences of murine and human miR-130a-3p (miR-130a) are identical. [score:1]
This corresponds well with observed effects of miR-130a on proliferation and cell cycle in immature neutrophil cells [9, 11]. [score:1]
At this point, the effect of miR-130a is reflected by differences between M and H proteins while light (L) proteins have all been synthesized prior to interference with the free miR-130a pool. [score:1]
This 32Dcl3 miR-130a clone was cultured in SILAC medium consisting of RPMI medium without arginine, lysine, and glutamine (PAA Cell Culture Company), 10 % dialysed FBS (Gibco), 100 U/mL penicillin and 100 μg/mL streptomycin (Gibco), 1 ng/mL murine IL-3 (Sigma-Aldrich), 1 % GlutaMAX™-1 (Gibco), and 0.2 mg/mL proline (Sigma-Aldrich) to avoid arginine-to-proline conversion [24]. [score:1]
a Cells grown in L medium were transfected with anti-miR-130a-LNA or scrambled-LNA (mock-transfection) and transferred to M or H SILAC-medium, respectively. [score:1]
This has previously been shown to be a good mo del for investigating the effect of miR-130a on specific target proteins [9, 11]. [score:1]
Other proteins that interact with this protein subset with protein-protein association probabilities above 0.7 and which have miR-130a association probabilities within the top 20 % were also included. [score:1]
Each protein was assigned a miR-130a association probability by mapping to RAIN [http://rth. [score:1]
For pSILAC, the 32Dcl3 miR-130a clone was grown in SILAC L medium for six days and subsequently washed twice with phosphate-buffered saline (PBS) to eliminate traces of L amino acids. [score:1]
Our aim was to evaluate the effect of miR-130a on the proteome at the time of neutrophil maturation when miR-130a expression is at its peak (myeloblasts and promyelocytes) [9]. [score:1]
Expression of miR-130a following transfection with an anti-miR-130a-LNA or scrambled-LNA of the 32Dcl3 miR-130a clone for 48 h (left) and Kasumi-1 cells for 72 h (right) measured by real-time PCR. [score:1]
Impact of miR-130a on protein output. [score:1]
Cells (5x10 [6]/condition) were then transfected with anti–miR-130a-LNA or scrambled-LNA (Exiqon) through electroporation using the AMAXA nucleofection system (program E-032) according to the manufacturer’s recommendations and transferred to M (anti–miR-130a-LNA) or H (scrambled-LNA) medium for approximately 48 h. Similarly, Kasumi-1 cells (human myeloblast cell line derived from a patient with acute myeloblastic leukemia, ATCC® CRL-2724) were grown in normal medium (RPMI1640 (Gibco), 20 % FBS (Gibco), 100 U/mL penicillin and 100 μg/mL streptomycin (Gibco)), washed twice with PBS before transfection (program C-23) with anti–miR-130a-LNA or scrambled-LNA (Exiqon) and switched to M or H SILAC medium, respectively, for approximately 72 h. The SILAC medium used for Kasumi-1 cells was identical to the 32Dcl3 SILAC medium except 20 % dialysed FBS was used and no IL-3 was added. [score:1]
After 48 h (32Dcl3 miR-130a clone, doubling time ~18–20 h) or 72 h (Kasumi-1, doubling time ~40 h) of pulse labelling, cells were washed, combined 1:1, and lysed. [score:1]
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[+] score: 329
We found that miR-130a gRNA and the miR-130a inhibitor decreased miR-130a expression, by 95% ± 1% (Fig. 3A and F) and 65% ± 3% (data not shown), respectively, and increased PKLR mRNA expression, by 2.37 ± 0.12- and 1.87 ± 0.1-fold (Fig. 3B and G), respectively, in Huh7.5.1 cells. [score:7]
It has previously been demonstrated that overexpression of miR-130a inhibits HBV DNA replication through targeting of PGC1α and PPARγ (13). [score:7]
FIG 2Overexpression of miR-130a inhibited PKLR expression and HCV replication. [score:7]
A miR-130a inhibitor and gRNA increased PKLR expression, HCV replication, and HBV replication, while miR-130a gRNA and PKLR overexpression increased HCV and HBV replication. [score:7]
Finally, we confirmed the inhibitory effect of miR-130a overexpression on PKLR mRNA (Fig. 2F) and HCV RNA (Fig. 2G) expression in JFH1-infected PHHs (Fig. 2E to H). [score:7]
FIG 4Overexpression of miR-130a inhibited PKLR expression and HBV replication. [score:7]
These genes were then validated by quantitative PCR (qPCR), and we found that the expression of three genes, encoding pyruvate kinase in liver and red cell (PKLR), interleukin-18 binding protein (IL18BP), and the low-density lipoprotein receptor (LDLR), was significantly downregulated by overexpression of miR-130a (by use of a miR-130a mimic) compared to that with the negative-control mimic treatment (data not shown). [score:7]
HCV infection is associated with increased miR-130a expression in human liver biopsy specimens and in an HCV infection cell culture mo del, and IFITM1 overexpression inhibits HCV replication (34). [score:7]
miR-130a expression has been reported to be upregulated in liver tissues of HCV-infected patients (34). [score:6]
A miR-130a hairpin inhibitor or CRISPR/Cas9 miR-130a gRNA was used to knock down miR-130a expression. [score:6]
Bhanja Chowdhury J, Shrivastava S, Steele R, Di Bisceglie AM, Ray R, Ray RB 2012 Hepatitis C virus infection modulates expression of interferon stimulatory gene IFITM1 by upregulating miR-130A. [score:6]
miR-338-3p suppressed the Warburg effects of hepatocellular carcinoma (HCC) cells by targeting PKLR (46), indicating that miR-130a likely plays a role in HCC development. [score:6]
miR-130a and its target genes were overexpressed or were knocked down by use of small interfering RNA (siRNA) or clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 guide RNA (gRNA). [score:6]
In contrast, knockdown of PKLR expression reduced HCV and HBV replication, and supplementation with pyruvate rescued the inhibitory effects of the miR-130a mimic and PKLR gRNA on virus infection. [score:6]
We therefore propose a miR-130a regulation pathway mo del in which miR-130a regulates HCV and HBV replication through PKLR expression and subsequent pyruvate metabolism. [score:5]
We applied four prediction algorithms, miRanda, RNAhybrid, TargetScan, and PITA, and obtained 2,152 potential target genes for miR-130a (https://drive. [score:5]
We confirmed that the miR-130a mimic (overexpression) decreased PKLR and HCV RNA and protein expression levels (Fig. 8C to F). [score:5]
We found that miR-130a mimic overexpression (Fig. 4A) downregulated the PKLR mRNA level 56% ± 6% compared to that with the negative-control mimic treatment in HepAD38 cells (Fig. 4B). [score:5]
FIG 3miR-130a gRNA and a miR-130a inhibitor increased PKLR expression and HCV replication. [score:5]
The bioinformatics analysis for identification of target genes of miR-130a was performed using the miRanda, RNAhybrid, TargetScan, and PITA software tools (57). [score:5]
We used bioinformatics software, including miRanda, TargetScan, PITA, and RNAhybrid, to predict potential miR-130a target genes. [score:5]
The miR-130a inhibitor, negative-control inhibitor, miR-130a gRNA, and negative-control gRNA were transfected into Huh7.5.1 cells. [score:5]
To verify whether the three possible target genes (PKLR, IL18BP, and LDLR) were direct target genes of miR-130a, a dual-luciferase reporter assay was performed. [score:5]
We confirmed that the PKLR gene is a direct target of miR-130a. [score:4]
To determine whether the PKLR, IL18BP, and LDLR genes are direct targets of miR-130a, we performed dual-luciferase mutation assays using the miR-130a (AGUGCAA) seed sequence as the binding sequence. [score:4]
Huang JY, Chou SF, Lee JW, Chen HL, Chen CM, Tao MH, Shih C 2015 MicroRNA-130a can inhibit hepatitis B virus replication via targeting PGC1alpha and PPARgamma. [score:4]
We identified PKLR as a direct target gene of miR-130a. [score:4]
These findings indicate that miR-130a regulates HCV replication through the targeting of PKLR in both an HCV JFH1 infection mo del and an HCV OR6 replicon mo del. [score:4]
The aims of our study were to identify miR-130a target genes and to define the molecular mechanism by which miR-130a regulates HCV and HBV replication. [score:4]
Of these, the gene encoding pyruvate kinase in liver and red blood cell (PKLR) was confirmed to be regulated by miR-130a overexpression. [score:4]
miR-130a regulates HCV replication through targeting of PKLR. [score:4]
These results confirm that miR-130a directly targets the 3′ UTR of PKLR. [score:4]
We concluded that miR-130a regulates HCV and HBV replication through its targeting of PKLR and subsequent pyruvate production. [score:4]
IMPORTANCE We identified that miR-130a regulates the target gene PKLR and its subsequent effect on pyruvate production. [score:4]
We sought to identify miR-130a target genes and to explore the mechanisms by which miR-130a regulates HCV and hepatitis B virus (HBV) replication. [score:4]
We found that miR-130a gRNA significantly knocked down miR-130a expression (Fig. 5A) and increased the PKLR mRNA level (Fig. 5B) in HepAD38 cells. [score:4]
miR-130a has been shown to regulate insulin sensitivity through targeting of GRB10 (44). [score:4]
miR-130a regulates HBV replication through targeting of PKLR. [score:4]
Supplemental pyruvate increased HCV and HBV replication and rescued the inhibition of HCV and HBV replication by the miR-130a mimic and PKLR knockdown. [score:4]
miR-130a overexpression (via a mimic) knocked down PKLR mRNA and protein levels. [score:4]
miR-130a regulated HCV and HBV replication through targeting of PKLR. [score:4]
Bioinformatic prediction of miR-130a targets. [score:3]
Supplemental pyruvate did not affect miR-130a expression. [score:3]
miR-130a gRNA significantly increased PKLR and HCV core protein expression in JFH1-infected Huh7.5.1 cells (Fig. 3D). [score:3]
The hLuc/Rluc ratio serves as a measure of the inhibition of luciferase expression due to the binding of miR-130a with each cloned 3′ UTR. [score:3]
miR-130a mimic, miR-130a inhibitor, siRNAs, CRISPR/Cas9 gRNAs, plasmids, and transfection. [score:3]
We found that overexpression of miR-130a led to PKLR reductions at both the mRNA and protein levels in Huh7.5.1 cells (Fig. 2A to D). [score:3]
A miR-130a mimic, a miR-130a hairpin inhibitor, and the corresponding negative controls were purchased from GE Dharmacon (Lafayette, CO, USA). [score:3]
Protospacer sequences for CRISPR/Cas9 targeting of miR-130a or PKLR were designed by use of CRISPR Design (http://crispr. [score:3]
We also observed a significant decrease in HCV core protein in JFH1-infected Huh7.5.1 cells after miR-130a overexpression (Fig. 2D). [score:3]
Interestingly, no significant change in cccDNA expression in HepAD38 cells was observed with either miR-130a mimic or miR-130a gRNA treatment (Fig. 4C and 5E). [score:3]
In addition, miR-130a expression and cell viability were not significantly affected by PKLR gRNA or supplemental pyruvate (Fig. 9D and E). [score:3]
Duan X, Guan Y, Li Y, Chen S, Li S, Chen L 2015 Vitamin D potentiates the inhibitory effect of microRNA-130a in hepatitis C virus replication independent of type I interferon signaling pathway. [score:3]
The miR-130a mimic reduced and the miR-130a inhibitor and gRNA increased HCV replication in OR6 cells (data not shown). [score:3]
Supplemental pyruvate (5 mM) rescued the inhibitory effect of the miR-130a mimic on HCV RNA replication reduction in JFH1-infected Huh7.5.1 cells (Fig. 8E). [score:3]
It has been reported that the interferon (IFN) -induced transmembrane protein IFITM1 is another potential miR-130a target (34). [score:3]
However, we found that neither PKLR gRNA (Fig. 6E) nor PKLR siRNA (data not shown) had an effect on miR-130a expression. [score:3]
miR-130a targets PKLR. [score:3]
As expected, we found that miR-130a knocked down increased HCV replication >2-fold in both the gRNA and miR-130a inhibitor treatment groups compared to that in the respective negative-control groups (Fig. 3C and H). [score:3]
FIG 8Pyruvate supplementation rescued the inhibitory effects of the miR-130a mimic on HCV and HBV replication. [score:3]
These results indicate that PKLR, not IL18BP or LDLR, is the target gene of miR-130a. [score:3]
Western blotting confirmed that miR-130a decreased the PKLR protein level and that pyruvate rescued HCV core protein expression (Fig. 8F). [score:3]
Using bioinformatics tools, we identified that miR-130a regulates PKLR. [score:2]
We found that miR-130a gRNA blocked IFN-stimulated response element (ISRE)-directed signaling (data not shown). [score:2]
Hepatitis C virus (HCV) infection has been shown to regulate microRNA 130a (miR-130a) in patient biopsy specimens and in cultured cells. [score:2]
We hypothesized that miR-130a regulates HCV and HBV replication through pyruvate metabolism. [score:2]
Li S, Duan X, Li Y, Liu B, McGilvray I, Chen L 2014 MicroRNA-130a inhibits HCV replication by restoring the innate immune response. [score:2]
We found that overexpression of miR-130a significantly repressed the hLuc/ Renilla luciferase (Rluc) ratio (by 45%) when miR-130a was cotransfected with the wild-type PKLR 3′ UTR (PKLR-3′UTR-WT) compared to that with the negative-control mimic (Fig. 1B). [score:2]
Further, we found that miR-130a regulates both HCV and HBV replication in addition to PKLR. [score:2]
After transient transfection of CRISPR/Cas9 gRNA into cells by use of Lipofectamine LTX reagent (Life Technologies), G418 (Life Technologies) was added for selection of miR-130a or PKLR knockdown cells. [score:2]
We clarified that miR-130a regulates HCV and HBV replication as well as PKLR, and therefore (likely) pyruvate metabolism. [score:2]
Our findings indicate that miR-130a regulation of the IFN -induced ISRE pathway and IFN-stimulated gene (ISG) innate immunity is independent of PKLR. [score:2]
These findings collectively indicate that miR-130a regulates HBV replication in HepAD38 cells and PHHs. [score:2]
We explored the regulatory effect of miR-130a on HCV replication in HCV JFH1-infected Huh7.5.1 cells and primary human hepatocytes (PHHs) and on HBV replication in HepAD38 cells (30) and HBV infectious supernatant-infected, sodium taurocholate-cotransporting polypeptide (NTCP) -transfected Huh7.5.1 cells or PHHs (31). [score:2]
In this study, we confirmed the regulatory effect of miR-130a on HCV and HBV. [score:2]
To confirm the direct binding between the 3′ UTR of PKLR and the miR-130a seed sequence, we mutated the 3′ UTR of PKLR by deleting the binding site of miR-130a. [score:2]
Our data provide novel insights into key metabolic enzymatic pathway steps regulated by miR-130a, including the steps involving PKLR and pyruvate, which are subverted by HCV and HBV replication. [score:2]
miR-130a gRNA or negative-control gRNA was transfected into HepAD38 cells for 72 h. (A) miR-130a gRNA decreased the miR-130a level. [score:1]
Cells were cotransfected with 50 nM miR-130a mimic (GE Dharmacon, USA) or 50 nM negative control (GE Dharmacon) and 0.1 μg/well plasmid by use of Lipofectamine LTX (Thermo, USA). [score:1]
The 3′ UTRs of PKLR, IL18BP, and LDLR were cloned downstream of the firefly luciferase (hLuc) reporter gene in the reporter vector pEZX-MT06, which was cotransfected with the miR-130a mimic or a negative-control mimic into Huh7.5.1 cells. [score:1]
miR-130a gRNA did not significantly affect cell viability (Fig. 5F). [score:1]
Moreover, we found that the miR-130a mimic decreased HBV cccDNA and total DNA levels, by 50% and 80%, respectively, in PHHs 72 h following HBV exposure (Fig. 4I and J). [score:1]
GenCRISPR gRNAs for miR-130a and PKLR were purchased from GenScript USA Inc. [score:1]
These findings indicate that PKLR lies downstream of miR-130a. [score:1]
The mutant PKLR reporter plasmid PKLR-3′UTR-Mut was constructed by deleting the binding sites of miR-130a in the 3′ UTR of PKLR. [score:1]
HCV JFH1 was inoculated into the appropriate wells and incubated for 48 h. (A) miR-130a gRNA decreased the miR-130a level. [score:1]
The miR-130a mimic modestly reduced the HBV covalently closed circular DNA (cccDNA) level (Fig. 4C) and significantly decreased total HBV DNA, by about 57% ± 3% in the HepAD38 cell supernatant (Fig. 4D) and by approximately 40% ± 2% in HepAD38 cells (Fig. 4E). [score:1]
In contrast, no significant changes were observed when miR-130a was cotransfected with an IL18BP-3′UTR-WT or LDLR-3′UTR-WT plasmid (Fig. 1C to E). [score:1]
*, P < 0.05; **, P < 0.01; #, P < 0.001 (for comparisons of the indicated miR-130a and negative-control mimic treatments without or with HCV JFH1 infection). [score:1]
The miR-130a mimic reduced HCV RNA (Fig. 8G) and HBV DNA (Fig. 8H and I) replication levels in PHHs. [score:1]
Western blotting confirmed that the miR-130a mimic reduced PKLR and HBcAg protein levels (Fig. 4G). [score:1]
However, the mechanisms by which miR-130a, HCV, HBV, PKLR, and pyruvate metabolism are interconnected remain elusive. [score:1]
The negative-control mimic or miR-130a mimic was transfected into Huh7.5.1 cells or primary human hepatocytes (PHHs). [score:1]
HBV from HepAD38 cells was used to infect cells for 72 h. miR-130a, HBV cccDNA, HBV DNA, and PKLR mRNA in cells, as well as HBV DNA in supernatants, were quantified using qPCR. [score:1]
The miR-130a mimic did not significantly affect the viability of PHHs (Fig. 2H). [score:1]
Western blotting confirmed that miR-130a gRNA increased the PKLR and HBcAg protein levels (Fig. 5G). [score:1]
Huh7.5.1 cells were cotransfected with a cloned pEZX-MT06 plasmid (containing PKLR-3′UTR-WT, PKLR-3′UTR-Mut, IL18BP-3′UTR-WT, or LDLR-3′UTR-WT) and a miR-130a mimic or negative-control (Neg) mimic. [score:1]
miR-130a, HCV RNA, and PKLR mRNA levels were tested by qPCR. [score:1]
A negative-control mimic or miR-130a mimic was transfected into HepAD38 cells or PHHs. [score:1]
The miR-130a mimic did not significantly affect the viability of Huh7.5.1 cells (Fig. 2C). [score:1]
The miR-130a level was normalized to the U6 level, and other selected gene mRNA levels were normalized to the GAPDH mRNA level, yielding arbitrary units (fold changes). [score:1]
The miR-130a mimic or negative-control mimic was transfected into Huh7.5.1 cells or PHHs. [score:1]
*, P < 0.05; **, P < 0.01; #, P < 0.001 (for comparisons of the indicated miR-130a and negative-control miRNA treatments). [score:1]
The miR-130a mimic did not significantly affect cell viability (Fig. 4F). [score:1]
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3
[+] score: 270
As shown in Fig. 4D, miR-130a/301a/454 inhibitor markedly enhanced TGFβ and BMP responses when the constitutively active form of TGF-β/BMP-receptor I (TβRI-ca/BMPRI-ca) was co-expressed, accompanied by Smad4 up-regulation, suggesting that miR-130a/301a/454 can suppress TGF-β/BMP signaling by inhibiting Smad4 expression. [score:14]
These data support the notion that over -expression of miR-130a/301a/454 leads to Smad4 down-regulation, thus inhibiting TGF-β signaling -mediated cell growth suppression, which contributes to the development of colon cancer. [score:11]
Among the putative target genes, Smad4, an important tumor suppressor involved in TGF-β/BMP signaling, was shown to contain a conserved putative miR-130a/301a/454 target site based on TargetScan prediction (Fig. 4A). [score:9]
To determine whether or not Smad4 is directly targeted by miR-130a/301a/454 expression, we constructed luciferase reporter plasmids containing Smad4 3′-UTR or bearing deletion/mutation of the putative miR-130a/301a/454 target site. [score:9]
Recently, miR-130a/301ab has been reported to be upregulated in several types of cancer, such as hepatocellular carcinoma, nonsmall cell lung cancer, chronic myeloid leukaemia, pancreatic cancer, and breast cancer [15]– [21]; however, miR-130a/301a is down-regulated in chronic lymphocytic leukemia and sickle cell anemia [22], [23], indicating the complexity and diversity of the roles of miR-130a/301a in tumorigenesis. [score:7]
By co-transfection with miR-130a/301a/454 mimic, we showed that the luciferase activity of the wild type Smad4-3′UTR reporter was suppressed, while the target site deleted or mutated reporter failed to be targeted by miR-130a/301a/454 co-transfection (Fig. 4B). [score:7]
As these miRNAs are able to enhance the tumorigenecity of colon cancer cells in vitro and in vivo, the target gene regulated by miR-130a/301a/454 can function as a tumor suppressor. [score:6]
Also, we cannot exclude the possibility that other potential targets of miR-130a/301a/454 may govern additional cancer pathways and promote the development of colon cancer, as a single miRNA is known to target multiple mRNAs. [score:6]
Tumor suppressor Smad4 is a direct target of miR-130a/301a/454. [score:6]
However, miR-130a is down-regulated in chronic lymphocytic leukemia, and can modulate cell survival by inhibiting the autophagy program [22]. [score:6]
In these cells, Smad4 expression was confirmed to be increased compared to control cells (Fig. 4E); however, miR-130a/301a/454 no longer targeted Smad4 expression, as these cells transcribed Smad4 mRNA without the 3′UTR. [score:6]
The known expression patterns, potential targets and biological functions of miR-130a/301a/454 family. [score:5]
The CCK8 assay showed that restoration of miR-130a/301a/454 significantly enhanced the proliferation of colon cancer HCT116 or SW480 cells (Fig. 2A and B), while over -expression of either inhibitor against miR-130a/301a/454 reduced cell viability in both colon cancer cells (Fig. 2C and D) These three miRNAs exhibited similar growth-promoting effects in colon cancers, and no mutual regulations among miR-130a/301a/454 were observed (Fig. 2E and F). [score:5]
The known patterns of expression, potential targets, and biological functions of this miR-130a/301a/454 family are summarized in Table 1 [15]– [23], [25]– [29]. [score:5]
To understand the clinical significance of miR-130a/301a/454 and its target in colon cancer, we determined the levels of miR-130a/301a/454 and protein expression of Smad4 in 14 pairs of matched colon cancer specimens by qRT-PCR and immunoblotting, respectively (Fig. 5A and B). [score:5]
We have discovered a novel target of miR-130/301/454 family (Smad4), which has key function in TGF-β signaling, providing the possibility that the miR-130/301/454 family may control reprogramming by suppressing TGF-β/Smad4 activity. [score:5]
The sequence alignments of miR-130a/301a/454 and its target sites in 3′UTR of Smad4, downloaded from TargetScan (http://www. [score:5]
These results further demonstrated that the growth-promoting roles of miR-130a/301a/454 were mainly through inhibition of Smad4 expression. [score:5]
These results suggest that miR-130a/301a/454 is up-regulated in colon cancer cells, which might be relevant to human colon cancer development. [score:5]
Furthermore, we determined whether or not the growth-promoting effects of miR-130a/301a/454 are mainly through targeting Smad4 expression. [score:5]
As expected, Pearson correlation coefficient analysis suggested that Smad4 expression was inversely correlated with miR-130a/301a/454 expression in colon cancer tissues (Fig. 5C–E). [score:5]
Moreover, miR-130a/301a/454 inhibitor failed to suppress cell viability in these cells (Fig. 4G). [score:5]
We demonstrated that miR-130a/301a/454 represses Smad4 expression through direct binding to 3′UTR, while we also noted that there are other miRNA consensus sites in the Smad4 3′-UTR (e. g., sites for miR-34a, miR-146a, and miR-199a, which have been identified as negative regulators of Smad4 in gastric cancer and glioblastoma) [33]– [35]. [score:5]
Hence, deregulation of miR-130a/301a/454 exists in distinct types of cancer, and the roles of this miRNA family in carcinogenesis and progression cannot be simply concluded as a tumor suppressor or oncogene. [score:4]
In the present study, we showed that miR-130a/301a/454 is up-regulated in colon cancer, and further demonstrated the proliferation-promoting effect of miR-130a/301a/454 in colon cancer cells. [score:4]
Recently, Pfaff et al. [25] showed that the miRNA family (miR-130/301/721) functions as an important regulator of iPSC induction by targeting the homeobox transcription factor, Meox2. [score:4]
We showed that miR-130a/301a/454 is up-regulated in clinically-resected human colon cancer tissues and colon cancer cell lines, and these miRNAs exhibit oncogenic properties in colon cancer cells in vitro and in vivo. [score:4]
In contrast, knockdown of miR-130a/301a/454 suppressed cell motility in colon cancer cells (Fig. 2G, right panel). [score:4]
To explore the roles of miR-130a/301a/454 in human colon cancer development, we detected the levels of expression in 35 pairs of human colon cancer and adjacent normal mucosa tissues. [score:4]
The human Smad4 3′UTR luciferase reporter plasmid and plasmid containing the miR-130a/301a/454 target site deleted or mutated Smad4 3′UTR were constructed as described previously [13]. [score:3]
0055532.g001 Figure 1The expression of miR-130a/301a/454 was examined by qRT-PCR in 35 paired human colon cancer and adjacent normal mucosa tissues (A, B, C), and in colon cancer cell lines as indicated (D, E, F). [score:3]
Moreover, there was a positive correlation between every two miRNAs among miR-130a/301a/454 (Fig. 1G–I), showing a common expression profile in this miRNA family in colon cancer. [score:3]
Notably, the growth-increasing effects of miR-130a/301a/454 were significantly suppressed in Smad4 -transfected HCT116 cells (Fig. 4F). [score:3]
Nevertheless, the pattern of expression and role of miR-130a/301a/454 in colon carcinogenesis remains unknown. [score:3]
Thus, the miR-130a/301a/454 family may represent a promising molecular target for the early detection of cancers. [score:3]
miR-130a/301a/454 inhibitor was introduced in HCT116 cells transfected with the TGF-β reporter CAGA12-lux or the BMP reporter BRE-lux. [score:3]
Clinical correlation between miR-130a/301a/454 levels and Smad4 expression. [score:3]
The expression of miR-130a/301a/454 was normalized to U6 in each sample. [score:3]
MiR-130a/301a/454 is up-regulated in colon cancer tissues and cell lines. [score:3]
Control RNA, miR-130a/301a/454 mimic or miR-130a/301a/454 inhibitor -transfected colon cancer HCT116 cells (A, B, C) and SW480 cells (D, E, F) were injected subcutaneously into either side of the posterior flank of the same nude mice, respectively (n = 8 per group). [score:3]
0055532.g004 Figure 4(A) Human Smad4 might be a molecular target of miR-130a/301a/454. [score:3]
The expression of miR-130a/301a/454 was examined by qRT-PCR in 35 paired human colon cancer and adjacent normal mucosa tissues (A, B, C), and in colon cancer cell lines as indicated (D, E, F). [score:3]
The different expression features of miR-130a/301a may reflect the diverse roles of the miR-130/301 family in different types of cancer. [score:3]
miR-130a/301a/454 expression was examined by qRT-PCR (B). [score:3]
MiR-130a/301a/454 was up-regulated in human colon cancer tissues and cell lines. [score:3]
These hypotheses indicate the need for further studies to reveal the entire “targetome” of the miR-130/301/454 family in colon carcinogenesis and progression. [score:3]
The correlation between miR-130a/301a/454 expression and the Smad4 protein level was analyzed using Pearson correlation coefficient analysis with r and p values, as indicated. [score:3]
Negative control RNA, miR-130a/301a/454 mimic or inhibitor transfected colon cancer cells, were injected into eight nude mice, as described. [score:3]
Exploring the expression profiles and roles of miR-130a/301a/454 in colon cancer will greatly expand our comprehension for this important miRNA family on tumorigenesis. [score:3]
MiR-130a/301a/454 directly represses the expression of Smad4. [score:3]
org), over a hundred genes are putative target genes for miR-130a/301a/454. [score:3]
The relative level of expression of miR-130a/301a/454 was normalized to the internal control (U6) using the 2 [−ΔΔCt] cycle threshold method. [score:3]
Normalized miR-130a/301a/454 and Smad4 protein levels of expression are shown as standardized values. [score:3]
The levels of miR-130a/301a/454 expression were validated by qRT-PCR assays from the tumor samples at the indicated times (Fig. 3G and H). [score:2]
According to qRT-PCR analysis, the levels of miR-130a/301a/454 expression were significantly increased in tumor tissues compared to adjacent normal mucosa tissues (Fig. 1A–C). [score:2]
In this study we investigated the expression and roles of miR-130a/301a/454 in colon cancer development. [score:2]
MicroRNA-130a/301a/454 is indicated as oncogenic miRNA in colon cancer development and progression, which is consistent with roles in other cancers, such as hepatocellular carcinoma, nonsmall cell lung cancer, chronic myeloid leukaemia, pancreatic cancer, and breast cancer [15]– [21]. [score:2]
In conclusion, our results confirm that the miR-130a/301a/454 family is a critical determinant in different kinds of cancer development and progression. [score:2]
The expression of miR-130a/301a/454 in tumor samples at the indicated times were detected using a qRT-PCR assay. [score:2]
Of note, immunoblotting analysis showed that miR-130a/301a/454 markedly reduced the level of endogenous protein expression of Smad4 compared to negative control RNA in HCT116 and SW480 cells (Fig. 4C). [score:2]
Inverse correlation between miR-130a/301a/454 and Smad4 protein level in colon cancer tissues. [score:1]
The high expression of miR-130a/301a/454 in colon cancer tissues and cell lines prompted us to investigate the biological function of these miRNAs in colon cancer. [score:1]
These results indicate that miR-130a/301a/454 significantly enhanced tumorigenicity of colon cancer cells in a nude mouse xenograft mo del. [score:1]
0055532.g003 Figure 3Effect of miR-130a/301a/454 on tumorigenicity in a nude mouse xenograft mo del. [score:1]
We further confirmed the tumor-promoting effects of miR-130a/301a/454 in vivo. [score:1]
Negative control or miR-130a/301a/454 mimic -transfected HCT116 or SW480 cells (1×10 [7]) were suspended in 0.1 ml PBS, then injected subcutaneously into either side of the posterior flank of the same 4-week-old female BALB/c athymic nude mice. [score:1]
As shown in Fig. 3, miR-130a/301a/454 -transfected HCT116 and SW480 cells had rapid tumor formation compared to negative control transfectants, while knockdown of miR-130a/301a/454 caused delayed tumor formation (Fig. 3A–F). [score:1]
Effect of miR-130a/301a/454 on tumorigenicity in a nude mouse xenograft mo del. [score:1]
MiR-130a/301a/454 promotes tumorigenecity in vivo We further confirmed the tumor-promoting effects of miR-130a/301a/454 in vivo. [score:1]
0055532.g002 Figure 2(A, B) Colon cancer HCT116 and SW480 cells were transfected with control RNA or miR-130a/301a/454 mimic as indicated. [score:1]
Thus, our data highlight the significance of the miR-130a/301a/454/family in cancer pathogenesis and suggest a potential application in cancer therapy. [score:1]
In addition, miR-130a/301a/454 was increased in colon cancer cell lines (HCT116, HCT15, HT29, SW480, and LoVo; Fig. 1D–F). [score:1]
These observations suggest that miR-130a/301a/454 promotes colon cancer cell growth and migration, thus acting as oncogenic miRNAs in colon cancer. [score:1]
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4
[+] score: 261
Several lines of evidence demonstrate that miR-130a directly targets c-myc mRNA: (1) Overexpression of miR-130a reduced the levels of c-Myc protein and mRNA, whereas inhibiting endogenous miR-130a significantly increased the levels of c-Myc protein and mRNA (Fig. 2); (2) miR-130a expression reduced the luciferase reporter activity in cells transfected with pGL3- c-myc 3′-UTR, but not the control pGL3 plasmid (Fig. 3A). [score:10]
Consistently, miR-130a has been shown down-regulated in multiple cancers [43, 44, 50] and leukemias [51], Together with our observation that miR-130a directly targets c-Myc, these results reveal that miR-130a may possess tumor suppressor function. [score:9]
Functionally, we show that overexpression of miR-130a significantly inhibited cell cycle progression and suppressed cell proliferation (Fig. 4). [score:7]
Conversely, suppression of endogenous miR-130a in U2OS cells by transfecting with miRIDIAN miR-130a hairpin inhibitor increased the levels of both c-Myc protein and mRNA as compared to the negative inhibitor control (Fig. 2C). [score:6]
Nevertheless, our results strongly suggest that upon UV irradiation, L11 recruits miR-130a -loaded miRISC to target c-myc 3′-UTR, leading to c-myc mRNA decay, demonstrating a novel mechanism underlying c-Myc downregulation in response to UV -induced DNA damage. [score:6]
U2OS (C) or WI38 (D) cells transfected with control or miR-130a hairpin inhibitors were assayed for the relative expression of c-myc mRNA normalized with GAPDH mRNA (middle panels) by RT-qPCR and c-Myc protein expression (bottom panels) by IB. [score:6]
Overexpression of miR-130a suppresses cell proliferation. [score:5]
These results indicate that miR-130a can suppress cell proliferation via targeting c-myc mRNA. [score:5]
Overexpression of miR-130a decreases both c-myc mRNA and protein and inhibits cell proliferation. [score:5]
As shown in Fig 4A and 4B, overexpression of miR-130a significantly reduced the percentage of S phase cells with the concomitant accumulation of G1 phase cells, indicating the inhibition of cell cycle progression by miR-130a. [score:5]
Interestingly, we found that L11 promotes the recruitment of miR-130a to c-myc mRNA to suppress c-Myc expression in response to UV irradiation. [score:5]
The miRIDIAN miR-130a mimic, negative control cel-miR-67 mimic, miRIDIAN miR-130a hairpin inhibitor and miRIDIAN microRNA inhibitor negative control were purchased from Dharmacon Inc. [score:5]
Figure 4 (A–B) Overexpression of miR-130a inhibits cell cycle progression. [score:5]
Herein, we have identified that miR-130a is a novel L11 -associated miRNA that suppresses c-Myc expression. [score:5]
miR-130a also targets ATG2B and DICER1 to inhibit autophagy and trigger killing of chronic lymphocytic leukemia cells (50). [score:5]
As shown in Fig. 3A, overexpression of miR-130a significantly reduced the luciferase activity in cells transfected with pGL3-myc-3′UTR, but not the control pGL3 vector, suggesting that miR-130a targets c-myc mRNA through its 3′-UTR. [score:5]
For example, miR-130a targets MET receptor tyrosine kinase to suppress lung cancer cell migration and promote TRAIL -induced apoptosis [43]. [score:5]
Figure 3miR-130a targets c-myc mRNA through its 3′-UTR (A) Overexpression of miR-130a reduces the activity of luciferase reporter with c-myc 3′-UTR. [score:5]
As shown in Fig. 3D, overexpression of miR-130a significantly reduced the luciferase activity in cells expressing pGL3-myc-3′UTR-FL or pGL3-myc-3′UTR-F1 plasmid containing the three putative miR-130a binding sites, whereas it did not significantly affect such activity in cells transfected with other pGL3 reporter containing c-myc 3′-UTR fragments lacking these sites (F2, F3 or F4) (Fig. 3D). [score:5]
miR-130a has recently been shown to suppress cancer cell growth and invasion through targeting the proto-oncogene MET [43] and several components in the mitogen-activated protein kinase (MAPK) pathway [44]. [score:5]
miR-130a has recently emerged as a key miRNA that inhibits cancer cell proliferation, invasion and migration by targeting other cellular proteins that promote cell proliferation or have oncogenic potential. [score:5]
Finally, we found that inhibiting miR-130a by the miR-130a inhibitor significantly abolished UV -induced reduction of c-Myc mRNA (Fig. 6I, compare the ratio of column 4 to column 3 with the ratio of column 2 to column 1) and protein (Fig. 6J, compare the ratio of lane 4 to lane 3 with the ratio of lane 2 to lane 1). [score:5]
Further, deletion of the first putative binding sites (BS-1, nt 21–42) (pGL3-myc-3′UTRΔBS1) with folding energy below the stringent cutoff (–25 Kcal/mol) [49] completely abolished the inhibition of luciferase activity upon miR-130a overexpression (Fig. 3D). [score:5]
We next asked whether miR-130a directly targets c-myc mRNA at its 3′-UTR. [score:4]
Thus, these results demonstrate that L11 plays an important role in c-Myc down-regulation in response to UV irradiation by promoting miR-130a -loaded miRISC to c-myc mRNA. [score:4]
Together, these results demonstrate that L11 promotes the recruitment of miR-130a -loaded miRISC to c-myc mRNA and down-regulates c-myc mRNA in response to UV irradiation. [score:4]
Knockdown of L11 (Figs. 5G and 5H) or inhibiting miR-130a (Figs. 6I and 6J) significantly blocked UV treatment -induced c-Myc reduction. [score:4]
Thus, miR-130a directly targets c-myc mRNA at its 3′-UTR. [score:4]
To determine the physiological relevance of the L11-miR-130a regulation of c-Myc, we asked whether L11 recruits miR-130a to target c-Myc in response to stress. [score:4]
In this study, we found that L11 recruits miR-130a-3p (miR-130a thereafter) to target c-myc mRNA following UV irradiation. [score:3]
To understand the biological function of miR-130a inhibition of c-Myc, we examined whether miR-130a affects cell proliferation. [score:3]
Together, these results suggest that miR-130a targets c-myc mRNA through binding to the BS-1 site. [score:3]
Under normal condition, miR-130a weakly associates with Ago2 and the basal level of c-myc mRNA targeting by Ago2 is minimal (Fig. 6), likely due to the lack of significant amount of free L11 or proper modification of L11. [score:3]
Similar effects were also observed in primary human fibroblast WI38 cells (Figs. 2B and 2D), suggesting that the inhibition of c-Myc by miR-130a is not cell type-specific effect. [score:3]
miR-130a, jointly with miR-203 and miR-205, targets several components in the MAPK and androgen receptor (AR) pathways to induce apoptosis and cell cycle arrest in prostate carcinoma cells [44]. [score:3]
miR-130a targets c-myc mRNA through its 3′-UTR. [score:3]
miR-130a targets c-myc mRNA through the c-myc 3′-UTR. [score:3]
Thus our results uncover a novel function of miR-130a in suppressing c-Myc in response to DNA damage. [score:3]
Alternatively, L11 binding may change the c-myc 3′UTR conformation, allowing the targeting by miR-130a/miRISC. [score:3]
U2OS cells transfected with control or miR-130a inhibitor were treated with or without UV. [score:3]
These results reveal that upon UV treatment, L11 promotes miR-130a -loaded miRISC to target c-myc mRNA. [score:3]
Figure 2 (A–B) Overexpression of miR-130a decreases c-Myc levels. [score:3]
The 5′ BS-1 (nt 21–42) region contains a loop structure (consistent with the recent finding that single stranded (loop) sites are more accessible for Ago2 binding and more likely to be true miRNA targets [53]), that is located close to the 3′ end in predicted secondary structure of c-myc 3′-UTR (not shown), suggesting that the secondary structure of the c-myc 3′-UTR is accessible to the L11-miR-130a-Ago2 complex. [score:3]
miR-130a inhibits cell proliferation. [score:3]
L11 recruits miR-130a to target c-myc mRNA in the cytoplasm. [score:3]
Upon UV irradiation, L11 is relocalized from the nucleolus to the cytoplasm where it targets miR-130a to c-myc mRNA (Fig. 7). [score:3]
UV damage induces the release of L11 from the nucleolus to the cytoplasm where it recruits miR-130a -associated RNA interference silencing complex (miRISC) to target c-myc mRNA at its 3′-UTR. [score:3]
To further confirm the miR-130a targeting of c-myc mRNA, we performed miR-130a transfection followed by RNA-IP using anti-Ago2 antibodies. [score:3]
Interestingly, although L11 recruits miR-24 to the c-myc 3′-UTR in response to ribosomal stress (22), the binding of L11 and Ago2 to miR-24 following UV treatment was much less robust compared to that of miR-130a (Figs. 6E and 6F), suggesting that miR-130a plays a prevalent role over miR-24 in c-Myc down-regulation in response to UV irradiation. [score:3]
Therefore, we tested whether miR-130a targets c-myc mRNA at these sites using luciferase reporters containing different fragments of c-myc 3′-UTR (Fig. 3C). [score:3]
U2OS (A) or WI38 (B) cells transfected with control or miR-130a mimics were assayed for the relative expression of miR-130a normalized with U6 snRNA (top panels), c-myc mRNA normalized with GAPDH mRNA (middle panels) by RT-qPCR, and c-Myc protein levels (bottom panels) by IB. [score:2]
293 cells transfected with control pGL3 or pGL3-myc-3′UTR in the presence of β-gal plasmid together with control or miR-130a mimic as indicated were assayed for the relative luciferase activity normalized to β-gal expression. [score:2]
RNAs extracted from the immunoprecipitates were assayed by RT-qPCR for a panel of miRNAs with potential tumor suppressor function, including miR-15a, miR-16, miR-130a, miR-107, miR-200b, and several let-7 family members including let-7a, let-7c, let-7f and miR-98 [35, 43– 48]. [score:2]
Further mapping analysis with pGL3- c-myc 3′-UTR mutants showed that miR-130a binds to the 5′ end BS-1 region (nt 21-42) in the c-myc 3′-UTR (Fig. 3D); (3) RNA-IP assays showed that c-myc mRNA was enriched in anti-Ago2 immunoprecipitates when miR-130a is overexpressed in cells (Fig. 3E). [score:2]
These data clearly indicate that miR-130a negatively regulates cell cycle progression and proliferation. [score:2]
As shown in Fig. 2A, overexpression of miR-130a significantly reduced the levels of both c-Myc protein and mRNA, compared to the negative mimic control, in U2OS cells. [score:2]
miR-130a regulates c-Myc levels. [score:2]
The cytoplasmic and the nuclear (Nuc) fractions isolated from U2OS cells treated with or without 40 J/m [2] UV for 6 hours were immunoprecipitated with anti-L11 antibodies or control rabbit IgG, followed by RT-qPCR detection of c-myc mRNA (B) and miR-130a (C). [score:1]
To verify this L11-miR-130a association, we performed similar RNA-IP experiments in cells transfected with Flag-L11 using IgG control. [score:1]
Of note, we have previously shown that L11 binds to the 3′-end of c-myc 3′-UTR [22] whereas miR-130a -binding site is located at the 5′-end of c-myc 3′-UTR (Fig. 3D), suggesting that structural accessibility contributes to this L11-recruited miR-130a- c-myc mRNA complex. [score:1]
We then examined whether L11 promotes the recruitment of the miR-130a -loaded miRISC to c-myc mRNA in response to UV treatment. [score:1]
U2OS cells were transfected with control or miR-130a mimic for 48 hours. [score:1]
UV treatment significantly increased the binding of L11 and Ago2 to miR-130a and c-myc mRNA as well as the interaction between L11 and Ago2 (Fig. 6). [score:1]
L11 associates with miR-130a. [score:1]
Our study also suggests that L11 acts as a stress -induced accessory factor to facilitate Ago2-miR-130a loading onto c-myc mRNA. [score:1]
Cells were transfected with pCMV-β-galactoside (β-gal) and luciferase reporter plasmid pGL3, pGL3-myc-3′UTR or its mutants, together with control or miR-130a mimic. [score:1]
These results indicate that in response to UV damage, L11 is released form the nucleolus to the cytoplasm where it recruits miR-130a/miRISC to the c-myc 3′-UTR, leading to c-myc mRNA decay. [score:1]
Lysates from 293 (B) and U2OS (C) cells transfected with Flag-L11 were immunoprecipitated with control mouse IgG or anti-Flag antibody, followed by RT-qPCR detection of miR-130a. [score:1]
To this end, U2OS cells were transfected with control or miR-130a mimic followed by cell cycle analysis. [score:1]
Indeed, miR-130a was specifically immunoprecipitated by anti-Flag antibody, but not control IgG, in both 293 (Fig. 1B) and U2OS (Fig. 1C) cells, suggesting that in cells. [score:1]
Figure 7UV irradiation promotes L11 interaction with miR-130a and c-myc mRNA in the cytoplasm (A) UV treatment releases L11 from the nucleolus into the nucleoplasm and the cytoplasm. [score:1]
Figure 6L11 recruits miR-130a -loaded miRISC to c-myc mRNA in response to UV irradiation (A) UV treatment increases the L11 binding to c-myc mRNA. [score:1]
UV irradiation promotes L11 interaction with miR-130a and c-myc mRNA in the cytoplasm. [score:1]
U2OS cells treated with or without UV were subjected to RNA-IP using control IgG or anti-Ago2 (E) or anti-L11 (F) antibodies, followed by RT-qPCR detection of miR-130a, miR-24 and the control U6 RNA. [score:1]
U2OS cells were transfected with control or miR-130a mimic as above. [score:1]
As shown in Figs. 3E and 3F, both miR-130a and c-myc mRNA, but not U6 or GAPDH mRNA, were significantly enriched in the anti-Ago2, but not the control IgG, immunoprecipitates in cells transfected with miR-130a mimic. [score:1]
To examine whether L11 promotes the recruitment of miR-130a -loaded miRISC to c-myc mRNA in response to UV, U2OS cells treated with or without UV were subjected to IP with anti-Ago2, anti-L11 antibodies, or control IgG. [score:1]
Our results here showed that UV also causes c-myc mRNA decay through an L11- miR-130a -mediated mechanism. [score:1]
L11 binding to miR-130a was also drastically increased in cells treated with UV (Fig. 6F). [score:1]
L11 promotes the recruitment of miR-130a to c-myc mRNA in response to UV treatmentWe then examined whether L11 promotes the recruitment of the miR-130a -loaded miRISC to c-myc mRNA in response to UV treatment. [score:1]
U2OS cells transfected with control or miR-130a mimic were subjected to RNA-IP using control IgG or anti-Ago2 antibody, followed by RT-qPCR detection of c-myc and GAPDH mRNA (E) as well as U6 and miR-130a (F). [score:1]
As shown in Fig. 1A, L11 bound strongly to miR-130a and to a less extent to miR-16, but not other tested miRNAs. [score:1]
L11 promotes the recruitment of miR-130a to c-myc mRNA in response to UV treatment. [score:1]
Although no conserved seed sequence for miR-130a binding was noted, analysis using RNA22 program as described [23], which allows seed mismatches [49], identifies three putative non-canonical “seedless” miR-130a binding sites (BS-1, BS-2, and BS-3) in the 5′ of the c-myc 3′-UTR with the miRNA:mRNA free folding energy cutoff –20 Kcal/mol (Fig. 3B). [score:1]
L11 recruits miR-130a -loaded miRISC to c-myc mRNA in response to UV irradiation. [score:1]
Figure 1 (A) Identification of miR-130a as a L11 -associated miRNA. [score:1]
We then searched for the potential miR-130a binding sites at the c-myc 3′-UTR. [score:1]
To verify that UV treatment promotes L11 binding to the c-myc 3′-UTR, we transfected 293 cells with pGL3, pGL3-myc-3′UTR-FL, or pGL3-myc-3′UTR-F1 plasmid as diagramed in Fig. 3C (the F1 fragment contains the miR-130a binding site, but lacks the L11 -binding site), followed by UV treatment. [score:1]
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NF-κB can increase miR-130a expression, and this enhancement of miR-130a expression inhibited TNF-α expression, which is a direct target of miR-130a. [score:12]
miR-130a directly targeted the 3’UTR of TNF-α and repressed its translation, and TNF-α activated NF-κB to upregulate miR-130a expression. [score:11]
Altogether, TNF-α initially stimulated NF-κB activation to induce miR-130a expression, which in turn targeted and down-regulated TNF-α expression and suggests a TNF-α/NF-κB negative feedback loop acting through miR-130a in cervical cancer cells (Figure 5G). [score:10]
Our findings indicate that TNF-α can activate NF-κB activity, which can reduce miR-130a expression, and that miR-130a targets and downregulates TNF-α expression. [score:10]
Thus, TNF-α stimulates NF-κB to induce miR-130a expression, and in turn, miR-130a downregulates TNF-α expression, which may form a feedback loop of TNF-α/NF-κB/miR-130a/TNF-α. [score:8]
TNF-α is a strong activator of NF-κB [42, 43], and our findings indicated that NF-κB could stimulate miR-130a expression, which in turn downregulated TNF-α expression (Figure 5A). [score:8]
miR-130a directly targets and negatively regulates TNF-α expression. [score:7]
In HeLa and C [33]A cells, NF-κB and miR-130a overexpression promoted cell growth, but genetic knockdowns suppressed growth. [score:6]
To confirm that miR-130a promotes cervical carcinoma cell growth through at least a partial downregulation of TNF-α, we generated a TNF-α expression vector (pcDNA3/TNF-α) lacking the TNF-α 3’UTR to minimize miRNA interference. [score:6]
TNF-α stimulates NF-κB to upregulate miR-130a expression to form a TNF-α/NF-κB/miR-130a feedback loop. [score:6]
Together, these data suggest that miR-130a downregulates TNF-α expression by binding to its 3’UTR. [score:6]
Hence, we found that NF-κB induced miR-130a expression to significantly increase, whereas the knockdown of NF-κB repressed miR-130a expression. [score:6]
To predict candidate target genes of miR-130a, we used three algorithm programs, TargetScan, PicTar, and miRanda. [score:5]
miR-130a was overexpressed or its endogenous expression was blocked in both cell lines, and total protein was harvested for analysis. [score:5]
Overexpression of miR-130a led to an approximately 50% reduction in TNF-α mRNA levels, but conversely, blocking miR-130a expression increased TNF-α mRNA levels by approximately 50% (Figure 3D). [score:5]
analysis showed that pcDNA3/pri-miR-130a reduced TNF-α protein expression levels by 40% in HeLa cells and 30% in C [33]A cells (Figure 3E), and blocking endogenous miR-130a expression increased TNF-α protein levels by 50% in both cells types (Figure 3F). [score:5]
In cancer, miR-130a targets MET in non-small cell lung carcinoma [40] and can target ATG2B and DICER1 to kill Chronic Lymphocytic Leukemia cells [41]. [score:5]
Furthermore, low TNF-α concentrations stimulated NF-κB activity and then induced miR-130a expression, and TNF-α overexpression rescued the effects of miR-130a on cervical cancer cells. [score:5]
Using these programs, we selected TNF-α as a miR-130a target gene for further study because of its ability to suppress cancer cell growth and to activate NF-κB. [score:5]
Therefore, we speculated that TNF-α may regulate miR-130a expression through the NF-κB pathway. [score:4]
TNF-α was identified as a target of miR-130a by binding in a 3’-untranslated region (3’UTR) EGFP reporter assay and by analysis. [score:4]
To elucidate miR-130a’s direct regulation of TNF-α, an enhanced green fluorescent protein (EGFP) reporter assay was used to identify the target site in the TNF-α 3’UTR. [score:4]
In Figure 2G and H, we seen NF-κB increased the growth capacity of crvical cncer cells through miR-130a, and we have demonstrated that miR-130a can direct targeting TNF-α, so we made a transfection of ASO-miR-130a and NF-κB, we found that the consume of miR-130a rescue the reduction of TNF-α inducted by NF-κB (Figure 5E), these results strongly support our hypothesis. [score:4]
Using human cervical cancer cell lines, this study aimed to investigate whether NF-κB could regulate miR-130a expression and the functions and targets of miR-130a. [score:4]
Altogether, these results indicate that miR-130a can bind to the TNF-α 3'UTR and negatively regulate its mRNA and protein expression levels. [score:4]
Moreover, TNF-α treatment upregulated miR-130a levels by approximately 5-6.5-fold in HeLa and C [33]A cells (Figure 5F). [score:4]
Furthermore, we examined endogenous TNF-α that had been downregulated by miR-130a. [score:4]
Numerous studies have shown that miR-130a plays an important role in cell function and carcinogenesis by targeting various genes, such as FOG-2 [36], GAX [37] and Smad4 [38] in cardiomyocytes, vascular smooth muscle cells and granulocytic precursors cells, respectively. [score:3]
This study is the first to demonstrate that NF-κB and miR-130a can promote the growth of human cervical cancer cells and identifies TNF-α as a new target gene of miR-130a. [score:3]
Low levels of TNF-α induced nuclear NF-κB translocation, which caused a gradual decline in miR-130a expression. [score:3]
Some reports have shown that miR-130a can mediate endothelial cancer cell growth [40, 41], and our data also showed that NF-κB enhanced the growth of cervical cancer cells and induced miR-130a expression. [score:3]
Therefore, these results provide further evidence that TNF-α overexpression counteracts the repressive effects of miR-130a on cell growth. [score:3]
showed that as miR-130a knockdown, cell growth ability decreased compare with the group only overexpressed NF-κB both in the MTT and colony formation assays (Figure 2G and H). [score:3]
A recent report showed that LPS could increase miR-130a expression, and NF-κB was involved in this process in human biliary epithelial cells [11]. [score:3]
When HeLa and C [33]A cells were transfected with pcDNA3/NF-κB or pSilencer/shR-NF-κB, qRT-PCR indicated that NF-κB overexpression increased the miR-130a levels by approximately 50% and 40% compared to that of control vector, but a knock down of NF-κB decreased the miR-130a levels by 25% in both HeLa and C [33]A cells, respectively (Figure 2A). [score:3]
TNF-α overexpression counteracts the effects of miR-130a. [score:3]
Moreover, ASO-miR-130a led to a suppression of cell viability and colony formation (Figure 2D and F) rate. [score:3]
To identify the miR-130a target genes responsible for its effects on cervical cancer cells, we used bioinformatics and functional knowledge associated with NF-κB and miR-130a and chose TNF-α as a candidate gene for further study. [score:3]
As miR-130a and NF-κB plays the same role on the growth of cancer cells, which prompt us miR-130a maybe one of the regulatory mechanisms of NF-κB, in order to verify this, we performed an experiment using by NF-κB in cells with miR-130a knockdown. [score:3]
Here, we found that TNF-α stimulated the nuclear translocation of NF-κB and induced miR-130a expression in HeLa and C [33]A cells. [score:3]
Therefore, we conclude that NF-κB promotes miR-130a expression. [score:3]
These results indicate that NF-κB may induce miR-130a expression. [score:3]
miR-130a, a miRNA has been shown to promote cell survival in several cell lines through different signaling mechanisms [36- 38], but its mechanism of action and expression are still not clear in cervical cancer. [score:3]
Hence, we shed light on the negative feedback regulation of NF-κB/miR-130a/TNF-α/NF-κB in cervical cancer and may provide insight into the carcinogenesis of cervical cancer. [score:2]
To construct a pcDNA3/pri-miR-130a vector expressing miR-130a, we amplified a DNA fragment carrying pri-miR-130a from genomic DNA using sense and antisense Pri-130a primers. [score:2]
Therefore, this NF-κB/miR-130a/TNF-a/NF-κB feedback signaling pathway may play an important role in the growth regulation of cervical cancer cells. [score:2]
We found that pcDNA3/pri-miR-130a expression led to a 25% decrease in EGFP fluorescence intensity compared with the control group, and the EGFP fluorescence intensity in cells transfected with ASO-miR-130a increased more than 25% (Figure 3B). [score:2]
In our previous experimental work, gene chip results showed some miRNAs which may regulated by NF-κB, miR-130a was in them and relatively few existing reports about it, so we picked it as our object of study for a further explore. [score:2]
In the EGFP reporter assay, the expression of an EGFP reporter plasmid containing the TNF-α 3’UTR was repressed by miR-130a, and the mutated TNF-α 3’UTR abolished this effect. [score:2]
miR-130a was overexpressed with TNF-α in HeLa and C [33]A cells, and then growth activity was examined by MTT and colony formation assays. [score:2]
These effects may result from miR-130a’s regulation of TNF-α requiring a certain length of time to be effective or involving other target genes; however, the detailed mechanism still needs to be investigated. [score:2]
Furthermore, qRT-PCR and analysis showed that miR-130a decreased TNF-α mRNA and protein expression levels in cervical cancer cells compared with the control. [score:2]
qRT-PCR revealed that cells transfected with pcDNA3/pri-miR-130a produced 7.5 and 6-fold increases in miR-130a levels. [score:1]
Similarly, the 3’UTR containing mutated miR-130a binding sites was amplified using PCR site-directed mutagenesis and cloned into the pcDNA3/EGFP plasmid between the same restriction sites with TNF-α-3’UTR-mut-sense and -antisense primers. [score:1]
In this study, we found that NF-κB and miR-130a promoted cervical cancer cell growth. [score:1]
Moreover, ectopic TNF-α expression lacking the 3’UTR abrogated the effects of miR-130a on cervical cancer cell growth in the colony formation assay, but cell viability assessed by MTT assay was not obviously affected. [score:1]
HeLa and C [33]A cells were co -transfected with the pcDNA3/TNF-α plasmid, which did not contain the TNF-α 3’UTR, with or without the pcDNA3/pri-miR-130a plasmid. [score:1]
Based on these results, we provide evidence of the existence of an NF-κB/miR-130a/TNF-α/NF-κB feedback loop in cervical cancer cells (Figure 5G). [score:1]
HeLa and C [33]A cells were co -transfected with pcDNA3/pri-miR-130a or ASO-miR-130a in a 48-well plate followed by the pcDNA3/EGFP-TNF-α-3’UTR or pcDNA3/EGFP-TNF-α-3’UTR-mut reporter plasmids. [score:1]
For in vivo tumor study, 3 × 10 [6] Hela cells transfected with pri-miR-130a and it is control vector were suspended in 150 μl of serum-free 1640 for each mouse. [score:1]
Therefore, this NF-κB/miR-130a/TNF-α feedback loop may contribute to low TNF-α concentrations that avoid the induction of apoptosis in carcinogenesis. [score:1]
Next, HeLa and C [33]A cells were cotransfected with the pcDNA3/EGFP-TNF-α-3’UTR reporter plasmid and pcDNA3/pri-miR-130a or ASO-miR-130a plasmids. [score:1]
However, ASO-miR-130a reduced miR-130a levels by almost 50% in transfected HeLa and C [33]A cells (Figure 2B). [score:1]
Figure 2 miR-130a promotes the growth of human cervical cancer cells. [score:1]
However, there were no significant changes in the fluorescence intensities of the pcDNA3/EGFP-TNF-α-3’UTR-mut group regardless of altered miR-130a levels (Figure 3C). [score:1]
HeLa and C [33]A cells were detached from 24-well plates after transfection with pcDNA3/pri-miR-130a or a control vector and ASO-miR-130a or control oligonucleotides, and the relative cell growth was determined at 24, 48 and 72 h after seeding in 96-well plates. [score:1]
We used the HeLa and C [33]A cervical cancer cell lines that were transfected with NF-κB or miR-130a overexpression plasmids to evaluate their effects on cell growth. [score:1]
First, we validated the efficiencies of pcDNA3/pri-miR-130a or miR-130a antisense oligomers (ASO-miR-130a). [score:1]
These results indicate that miR-130a facilitates HeLa and C [33]A cell viability and growth, which is consistent with NF-κB’s effects on HeLa and C [33]A cells. [score:1]
Therefore, we conclude that miR-130a promotes cell growth through at least the partial involvement of TNF-α. [score:1]
Thus, we speculated that miR-130a may mediate NF-κB’s cell growth effects. [score:1]
The complementary sequence between the seed sequence of miR-130a and the TNF-α 3’UTR is shown in Figure 3A. [score:1]
analysis showed that the miR-130a -induced reduction in TNF-α levels was rescued by the pcDNA3/TNF-α plasmid transfected into HeLa and C [33]A cells (Figure 4A and B). [score:1]
We first constructed an EGFP reporter plasmid by inserting the miR-130a binding site in the TNF-α 3’UTR downstream of the EGFP stop codon (pcDNA3/EGFP-TNF-α-3’UTR) and a mutant seed sequence in a reporter plasmid (pcDNA3/EGFP-TNF-α-3’UTR-mut). [score:1]
NF-κB promotes human cervical cancer cell growth through miR-130a. [score:1]
Cells were transfected with pcDNA3/NF-κB and ASO-miR-130a compare pcDNA3/NF-κB and ASO-NC, the cells were collected totle protein for Western Blot. [score:1]
Thus, TNF-α can stimulate NF-κB activity and enhance miR-130a levels, which then reduces TNF-α levels. [score:1]
We also verified this result in vitro, cells were transfected with pcDNA3/pri-miR-130a and its control vector then injected subcutaneously in the flank and collected the tumor tissue. [score:1]
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Other miRNAs from this paper: hsa-mir-130b
In both mo dels of pulmonary (bleomycin exposure) and liver (CCl [4] exposure) fibrosis, Short-130 inhibited miR-130/301 and reversed the down-regulation of miR-130/301 target genes Pparγ and Lrp8 (Figs 5 and 6C), decreased Lox expression, reduced collagen expression and collagen crosslinking (Figs 5C,E,F and 6C,E,F), and reduced Yap nuclear localization (Figs 5C and 6C) and YAP activation, as reflected by CTGF expression (Fig. 5E and 6E). [score:14]
Second, such pitfalls may be exaggerated by the widespread but cell-type specific functions of this miRNA family beyond the fibroblast, presumably dictated by a non-identical cohort of miR-130/301-specific target genes active in differing cell types 9. Nonetheless, selective pharmacologic targeting of the fibroblast in specific disease conditions holds promise, and future biological confirmation of the broader, network -based actions of miR-130/301 family could further guide such a systems pharmacology approach to targeting fibrosis which has not yet been pursued in great depth. [score:9]
To demonstrate the putative unifying biology of miR-130/301 in this cohort of physiologic states, pulmonary fibrosis (Index Diseases #11 and #19, Table S1) and fibrotic liver disease (Index Disease #4, Table S1) were selected for further interrogation. [score:7]
Consistent with our prior findings of a positive feedback loop in PH involving YAP/TAZ-miR-130/301 that both initiates and results from ECM stiffening 9, GW3965 treatment also reduced YAP nuclear localization (Fig. 7A) and YAP activation, as reflected by decreased Ctgf expression (Fig. 7C), as well as reversed Pparγ and Lrp8 down-regulation (Fig. 7A). [score:6]
In the lung of mice treated with bleomycin, miR-130a expression was up-regulated in parenchymal fibroblasts, as demonstrated by co-localization of miR-130a with vimentin, a fibroblast marker, and α-smooth muscle actin (α–SMA), a marker of both activated fibroblasts and smooth muscle cells (Fig. 2D). [score:6]
This protocol led to up-regulated miR-130a expression (but not other family members) in whole liver tissue (Fig. 4A). [score:6]
Alternatively, if certain fibrotic disease states exist (i. e., potentially at earlier time points of disease progression or specific clinical subtypes) where individual molecules are activated in isolation such as miR-130/301 or ApoE, more tailored therapy could be attempted and may be effective in those cases. [score:5]
Network analysis reveals that miR-130/301 members target a shared cohort of fibrotic genes across human diseases and physiologic states related to PH. [score:5]
We previously demonstrated that forced expression of miR-130/301 in the lung of mice is sufficient to induce pulmonary hypertension 12 and pulmonary vessel fibrosis 9. To determine if miR-130a is sufficient to induce liver fibrosis, chronic liver expression of miR-130a was studied. [score:5]
Furthermore, consistent with the direct down-regulation of the associated factors peroxisome proliferator-activated receptor gamma (PPARγ), apolipoprotein E (APOE) and the apolipoprotein E receptor LRP8 by miR-130/301 in PH 9, both Pparγ and Lrp8 were decreased in pulmonary fibrosis (Fig. S1). [score:5]
In regard to the relationship of this disease network to PH specifically, identification of the centrality of the YAP/TAZ-miR-130/301 circuit also provides molecular insight into the heterogenous clinical associations of secondary diseases found with this enigmatic vascular condition 54. [score:5]
Inhibition of the miR-130/301 family prevents ECM remo deling and disease progression in mouse mo dels of pulmonary fibrosis and liver fibrosis. [score:5]
Especially since YAP/TAZ and miR-130/301 appear to activate a positive feedback loop for robust ECM stiffening at least in PH 9, a pharmacologic combination of miR-130/301 inhibition via shortmers 59 in addition to manipulating downstream miR-130/301 -dependent pathways such as LXR/APOE activity (Fig. 7) offers a rational avenue for cooperative therapeutic targeting of fibrosis. [score:5]
It not only suggests the utility of related pharmacologic strategies (i. e., inhibitors of miR-130/301) for such associated diseases but also the importance of selective use to avoid unintended detrimental consequences of manipulating a pathway so broadly shared among fibrotic processes. [score:5]
Similarly, as guided by our network predictions regarding various fibrotic liver diseases (for instance, Index Disease #4, Table S1), miR-130a and YAP were found to be increased in fibrotic human liver tissue – in this case stemming from nonalcoholic steatohepatitis (Fig. 3E patient demographics in Table S4). [score:5]
Coupled with the top ranking of this miRNA family by spanning score in relation to the fibrosis network directly (Fig. 1B), these findings predicted that miR-130/301 members are integral to the fibrotic program across a variety of diseases and tissue beds. [score:4]
To define the exact cell types in which miR-130/301 was up-regulated, an in situ protocol was developed to stain simultaneously for miRNA and protein (see ). [score:4]
First, because fibrosis and matrix production also have positive and adaptive attributes in certain conditions (i. e., normal wound healing and organ development), inhibition of miR-130/301 may have substantial pitfalls, if used in non-selective contexts. [score:4]
First, these diseases may develop in a cell autonomous fashion, driven by separate injuries [such as hypoxia, inflammation, and specific genetic mutations linked to PH 12] that induce miR-130/301 in distinct tissue beds. [score:4]
Thus, it is tempting to speculate that genetic mutations linked to PH and miR-130/301 9 may also contribute to separate fibrotic lung and liver diseases. [score:4]
Our results showcase the power of advanced analysis of gene network architecture not only to predict a relevant fibrotic gene “program” shared among related human diseases and physiologic states but also to identify its overarching regulators, such as the miR-130/301 family, across those conditions (Figs 1 and 7D). [score:4]
These effects were enhanced by delivery of both miR-130a along with a decreased dose of CCl [4], promoting a robust down-regulation of Lrp8 and Pparγ and more substantially increased Yap1 activation and collagen crosslinking, compared to CCl [4] alone, CCl [4]+miR-control (miR-NC), or miR-130a alone (Fig. 4C,D). [score:3]
Forced expression of miR-130a in liver tissue of mice. [score:3]
Positive correlation of ECM stiffening and YAP/TAZ -dependent expression of miR-130/301 in mice and humans suffering from lung fibrosis. [score:3]
Moreover, forced miR-130a and increased ECM stiffening was sufficient to activate a self-amplifying feedback loop and further increase endogenous miR-130/301 family expression (Fig. 4A). [score:3]
Utilizing an in silico “fibrosis network” 9 composed of curated seed genes known to be causatively involved in ECM remo deling and their first degree interactors (Fig. 1B), we found a broad and diverse contingent of factors related to ECM remo deling within the predicted pool of miR-130/301 target genes and their related network neighbors. [score:3]
Moreover, by offering proof of our in silico predictions, these findings identify the fibrotic actions of the miR-130/301 family as a unifying molecular basis for the convergent relationship of seemingly disparate diseases (Fig. 7D). [score:3]
Forced miR-130/301 expression activates ECM remo deling and liver fibrosis in mice. [score:3]
The coupling of such network -based mo deling with experimental validation also facilitated the identification of the YAP/TAZ-miR-130/301 circuit as a broad mediator of mechanotransduction across a variety of tissue beds and disease contexts. [score:3]
Similarly, in a mouse mo del of carbon tetrachloride (CCl [4]) -induced liver fibrosis (Fig. 3), miR-130/301 was increased (Fig. 3A,B) and Pparγ and Lrp8 were correspondingly decreased (Fig. S2), accompanied by a positive correlation among collagen crosslinking, miR-130a expression, and YAP nuclear localization (Fig. 3C). [score:3]
Positive correlation of ECM stiffening and YAP/TAZ -dependent expression of miR-130/301 in mice and humans suffering from liver fibrosis. [score:3]
In that vein, our network analysis also uncovered shared miR-130/301-specific commonalities among diseases that have rarely, if ever, been clinically associated with fibrosis (i. e., Ebola infection, schizophrenia, among others; Table S1). [score:3]
In doing so, miR-130/301 inhibition significantly reduced end-stage fibrosis, as assessed by Metavir (Fig. 5D) score and Ashcroft score (Fig. 6D). [score:3]
Moreover, consistent with the known relevance of miR-130/301 in PH 12, among the 137 networks described above, a subset, ranked highly by their interconnectedness with the fibrosis network and the miR-130/301 family (Table S1, S3), was found to share a distinct cohort of fibrotic genes embedded in the overlap with a previously reported 12 PH disease gene network (Fig. 1D, Table S3). [score:3]
To determine whether miR-130/301 family members are necessary for control of fibrosis across both pulmonary and liver fibrosis, mice were serially administered control versus Short-130, an antisense oligonucleotide confirmed to inhibit all miR-130/301 family members in cultured cells 12 and in vivo in mouse liver (Fig. 5A,B) and mouse lung (Fig. 6A,B). [score:3]
Inhibition of miR-130/301 in a mouse mo del of liver fibrosis. [score:3]
Furthermore, it is possible that an even more complex and wide-reaching interactome exists among miR-130/301 and additional miRNAs predicted to recognize large portions of the same fibrotic disease network (Fig. 1, Table S2). [score:3]
By using network -based computational mo deling and in vivo experimentation, we have defined the YAP/TAZ-miR-130/301 molecular circuit and its downstream control of ECM remo deling as a shared and unifying in vivo origin of a network of human diseases and physiologic conditions (Fig. 7D). [score:3]
Consistent with induction of miR-130/301 by the mechanosensitive YAP/TAZ transcription factors in PH 9, a positive correlation was observed among miR-130a expression, YAP nuclear localization, and downstream collagen crosslinking in pulmonary fibrosis (Fig. 2C). [score:3]
Together, the results herein define the control of a fibrotic gene program by the YAP/TAZ-miR-130/301 circuit, shared among a network of related diseases. [score:3]
Correspondingly, as predicted by our network algorithm (Index Diseases #11 and #19, Table S1), the same relationships between miR-130/301, YAP/TAZ, and collagen crosslinking were observed in pulmonary tissue derived from a cohort of patients suffering from idiopathic pulmonary fibrosis (Fig. 2E,F, Fig. S1). [score:3]
Thus, a combination of network analyses predicted a unique position for the miR-130/301 family at the intersection of fibrotic gene programming and this set of associated diseases and physiologic states. [score:3]
miR-130/301 was ranked among the top five miRNAs, underlining its importance to diseases with a strong fibrotic component (red box). [score:3]
miR-130/301 inhibition ameliorates pulmonary fibrosis. [score:3]
Thus, as delineated by our in silico predictions, distinct from PH, the YAP/TAZ-miR-130/301 circuit is activated across both pulmonary and hepatic diseases in animals and humans. [score:3]
Inhibition of miR-130/301 in a mouse mo del of pulmonary fibrosis. [score:3]
In mouse mo dels of bleomycin -induced pulmonary fibrosis (Fig. 2), miR-130/301 expression was increased (Fig. 2A,B). [score:3]
miR-130/301 expression correlates with activation of YAP/TAZ, the PPARY-APOE-LRP8 axis, and matrix stiffening in pulmonary fibrosis and liver fibrosis. [score:3]
miR-130/301 overexpression activates ECM remo deling and liver fibrosis progression in mouse. [score:3]
How to cite this article: Bertero, T. et al. A YAP/TAZ-miR-130/301 molecular circuit exerts systems-level control of fibrosis in a network of human diseases and physiologic conditions. [score:3]
Eight-week-old mice (C57Bl6) were injected with bleomycin (1.5U/kg Sigma Aldrich) followed by 10 intraperitoneal injections (every 2 days) of control or miR-130/301 shortmer oligonucleotides, designed as antisense inhibitors recognizing the seed sequence of this miRNA family (20 mg/kg/dose; Regulus). [score:3]
miR-130/301 inhibition ameliorates liver fibrosis. [score:3]
In a mo del of lung fibrosis (bleomycin-induction), mice were treated with control (Short-NC) or miR-130/301 inhibitor (Short-130) (n = 8/10 per group). [score:3]
miR-130/301-specific fibrotic activity is active throughout a network of human diseases and physiologic conditions. [score:3]
Via in situ liver stain of mice treated with CCl [4], miR-130a expression co-localized with both desmin, a stellate cell marker, and α–SMA (Fig. 3D). [score:3]
miR-130/301 was ranked among the top five miRNAs by spanning score in this network (targets encircled in black), reflecting its robust, systems-level control over fibrosis and matrix remo deling. [score:3]
Upon identifying the miR-130/301 family as a critical regulator of fibrosis across contexts, we ranked each of the 137 networks according to (a) its overlap with the fibrosis network and (b) the spanning score rank assigned to miR-130/301 in that context. [score:2]
Unlike prior studies of miR-130/301 family members focusing on specialized conditions such as liver cancer 45 46, breast cancer 47 48, scleroderma 49, our findings here emphasize the global dysregulation of the miR-130/301 family and its elusive interconnections with the molecular fibrotic machinery of the fibroblast. [score:2]
Consequently, we can conclude that the YAP-TAZ-miR-130/301 circuit acts as a master regulator of both fibrotic gene programming and ECM remo deling across multiple pathobiological contexts in vivo. [score:2]
MiR-130a expression was quantified in the vascular wall of 15–20 pulmonary arteries or for liver tissue in 10 random 20x fields per animal using ImageJ software (NIH). [score:2]
MiRNA delivery was achieved by serial (every 3 days during 4 weeks) intraperitoneal injections of liposomally encapsulated miR-130a oligonucleotide mimics in presence or absence of suboptimal dose of CCl [4] (0.1 mL per kg body by week). [score:1]
Desmin/miR-130a and a–SMA/miR-130a positive cells were increased in CCl [4] -treated liver (n = 8 per groups; 5 20X fields per slide were quantified). [score:1]
Immunohistochemistry also revealed that miR-130a decreased Lrp8 and Pparγ as well as slightly increased YAP nuclear localization and collagen deposition and crosslinking. [score:1]
Moreover, given increased miR-130/301 levels in plasma of PH patients 12 56, pathogenic transfer and endocrine signaling of miR-130/301 between lung and liver is an intriguing possibility. [score:1]
Vimentin/miR-130a and α–SMA/miR-130a positive cells were increased in bleomycin -treated lung tissue (n = 8 per groups; 5 20X fields per slide were quantified). [score:1]
Specifically, 5 μm tissues sections were probed using a 3′ fluorescein isothiocyanate (FITC) labeled miRCURY LNA hsa-miR-130a detection probe (Exiqon; 5′-ATGCCCTTTTAACATTGCACTG-3′). [score:1]
Pharmacologic activation of APOE with LXR agonist GW3965 decreases peri-arteriolar fibrosis and improves lung fibrosis in vivoTo determine whether downstream ApoE is critical for miR-130/301 -induced fibrosis, we attempted to prevent lung fibrosis in bleomycin-exposed mice via treatment with a pharmacological activator of ApoE 13, the liver-X nuclear hormone receptor agonist GW3965 (Fig. 7). [score:1]
Eight-week-old mice (C57BL/6) were injected by intraperitoneal route every 3 days during 6 weeks with 1 nmol of miR-control (pre-miR-NC) or miR-130a (pre-miR-130a) (Thermo Fisher Scientific/Life Technologies) mixed in 100 μl PBS solution containing 5% Lipofectamine 2000 (Thermo Fisher Scientific/Life Technologies). [score:1]
Moreover, miR-130a+CCl [4] more robustly decreased Lrp8 and Pparγ as well as more robustly increased YAP nuclear localization, collagen deposition, and crosslinking. [score:1]
Taken together, consistent with the miR-130a -dependent actions in the pulmonary vascular space, these results demonstrated that this miRNA is sufficient to induce liver fibrosis as well. [score:1]
Conditions in red were ranked highly based on their interconnectedness with the fibrosis network and the miR-130/301 family (top 25%, as ranked in Table S1), and all were found to share a distinct cohort of fibrotic genes embedded in the overlap with the PH network. [score:1]
This was quantified as the average of two values: (1) the fraction of network genes that were shared with the fibrosis network and (2) the fraction of the highest possible rank achieved by miR-130/301 [1 – rank [130]/rank [MAX]]. [score:1]
For instance, in WHO Group III PH associated with pulmonary fibrosis, our results indicate that, independent of hypoxia, parenchymal fibrosis may activate the YAP/TAZ-miR-130/301 circuit in adventitial fibroblasts and perhaps other related mesenchymal stem cells 55, thus accelerating vascular stiffness. [score:1]
Given its adjustable, feedback -driven property, the miR-130/301-YAP/TAZ circuit may be responsible, in part, for individualized “tuning” of ECM remo deling observed among different fibrotic disorders. [score:1]
miR-130/301 was significantly increased by RT-qPCR (A), and serial sections of lung (B) displayed increased collagen (Picrosirius Red), miR-130a, and YAP by in situ hybridization. [score:1]
Thus, beyond PH, the YAP/TAZ-miR-130/301 feedback loop is active in pulmonary fibrosis and specifically in fibroblasts anatomically far removed from the pulmonary vasculature itself. [score:1]
To determine whether downstream ApoE is critical for miR-130/301 -induced fibrosis, we attempted to prevent lung fibrosis in bleomycin-exposed mice via treatment with a pharmacological activator of ApoE 13, the liver-X nuclear hormone receptor agonist GW3965 (Fig. 7). [score:1]
The prevalence of fibrotic states predicted to involve miR-130/301 provides evidence for a shared fibrotic program controlled by this miRNA family in a wide range of human pathology and conditions beyond the pulmonary vasculature (see Table S3). [score:1]
Given our growing appreciation of YAP/TAZ activity resulting from physical stimuli such as shear stress 50, it is also possible that miR-130/301 and other YAP/TAZ -associated miRNAs may constitute a newly defined set of factors responding to a wide range of physical alterations (i. e., vascular hemodynamics) of the microenvironment in addition to stiffness alone. [score:1]
The putative connection of miR-130/301 and ECM biology to schizophrenia is particularly intriguing, as it is a disorder where ECM remo deling in perineuronal nets is already suspected to control final psychiatric manifestations 17. [score:1]
Eight-week-old mice (C57Bl6) were injected with CCl [4] (1mL per kg of body weight) every 5 days accompanied by intraperitoneal injections (every 2 days) of control or miR-130/301 shortmer oligonucleotides (20mg/kg/dose; Regulus). [score:1]
Although it appeared that many miRNAs may have relevant actions in fibrosis, with these data, we identified miR-130/301 family members among the most highly ranked miRNAs (Rank #4) with a robust one-way inverse correlation (one way ANOVA) between their assigned spanning score rank and the size of the fibrotic component for each of the 137 networks (Fig. 1C, Table S2). [score:1]
Given the importance of the YAP/TAZ-miR-130/301 circuit in PH 9, we postulated that this feedback loop may be similarly active in controlling ECM plasticity in other fibrotic states. [score:1]
[1 to 20 of 83 sentences]
7
[+] score: 223
Other miRNAs from this paper: hsa-mir-130b
HCAECs in the logarithmic growth phase were divided into eight groups: the blank group (without any treatment), the negative control (NC) group (transfected with empty vector), the miR-130a mimics group (transfected with miR-130a analogue), the miR-130a inhibitors group (transfected with miR-130a inhibitors), the si-PTEN group (transfected with si-PTEN), the Wortmannin group (Wortmannin [a PI3K inhibitor] was incubated with the cells for 24 h), the miR-130a inhibitors + si-PTEN group (co -transfected with miR-130a inhibitors and si-PTEN) and the miR-130a mimics + Wortmannin group (after transfection with miR-130a analogue for 6–8 h, the culture solution was changed to complete culture medium, and then Wortmannin was also incubated with the cells for 24 h). [score:11]
Based on the above results, the high level of HCY was an independent risk factor for coronary heart disease (CHD), and miR-130a expression was decreased, and PTEN expression was increased in HCAECs treated with high concentrations of HCY, which then inhibited the PI3K-Akt-eNOS signaling pathway. [score:9]
analysis results demonstrated that compared with the blank and the NC groups, the protein expressions of PTEN were significantly increased in the miR-130a mimics, si-PTEN and miR-130a mimics +Wortmannin groups, and the protein expression of PTEN was significantly decreased in the miR-130a inhibitors group (all P < 0.05), while no significant difference was found between the Wortmannin group and the miR-130a inhibitors + si-PTEN group (P > 0.05). [score:8]
The relative expressions of miR-130a in the supernatants of cells treated with HCY at concentrations of 0.25, 0.5 and l. 0 mmol/L were significantly lower while the expression of PTEN mRNA was higher than those in the control group (0 mmol/L), except for the 0.1 mmol/L HCY condition (P < 0.05), and the content of miR-130a in the cell supernatant decreased with increasing HCY concentrations while the expression of PTEN mRNA increased with increasing HCY concentrations (both P < 0.05) (Figure 5). [score:7]
The concentrations of these inflammatory factors in the miR-130a inhibitors group were higher than those in the miR-130a inhibitors + si-PTEN group, and in the si-PTEN group were lower than those in the miR-130a inhibitors + si-PTEN group (all P < 0.05). [score:7]
Previous study has claimed that miR-130a could down-regulate the expression of PTEN in ECs [35]. [score:6]
Compared with the miR-130a inhibitors + si-PTEN group, the mRNA expression of PI3K was lower in the miR-130a inhibitors group while were higher in the si-PTEN group (both P < 0.05). [score:6]
The results demonstrated that compared with the blank and the NC groups, the mRNA expressions of miR-130a in the miR-130a mimics and the miR-130a mimics +Wortmannin groups were significantly increased while were significantly decreased in the miR-130a inhibitors and the miR-130a inhibitors + si-PTEN groups (all P < 0.05). [score:6]
Compared with the miR-130a inhibitors + si- PTEN group, the protein expressions of PI3K, p-PI3K, p-Akt, and p-eNOS and the ratios of p-PI3K/PI3K, p-Akt/Akt and p-eNOS/eNOS were significantly decreased in the miR-130a inhibitors group while increased in the si-PTEN group (all P < 0.05). [score:6]
The cell activity in the miR-130a inhibitors group was lower while in the si-PTEN group was higher than that in the miR-130a inhibitors + si-PTEN group (P < 0.05) (Figure 9). [score:5]
Figure 5(A) Effect of different doses (0, 0.1, 0.25, 0.5 and l. 0 mmol/L) of HCY on the relative expression of miR-130a in HCAEC cells; (B) Effect of different doses (0, 0.1, 0.25, 0.5 and l. 0 mmol/L) of HCY on the relative expression of PTEN mRNA in HCAEC cells. [score:5]
The Lipofectamine 2000 solution was prepared with 1 μl Lipofectamine 2000 + 50 μl serum-free medium and placed at room temperature for 5 min, and the miR-130a inhibitor was prepared with miR-130a inhibitors (20 pM) + 50 μl serum-free medium and placed at room temperature for 20 min. [score:5]
Previous evidence has shown that miR-130a suppresses PTEN expression, leading to the activation of PI3K/Akt signaling [26], which was consistent with our results. [score:5]
No significant difference was found in the mRNA expression of PTEN between the Wortmannin and the miR-130a inhibitors + si-PTEN groups (P > 0.05). [score:5]
MiR-130a has recently emerged as a key miR that inhibits cancer cell proliferation, invasion and migration by targeting other cellular proteins that promote cell proliferation or have oncogenic potential [27]. [score:5]
The apoptotic rate was higher in the miR-130a inhibitors group while was lower in the si-PTEN group than that in the miR-130a inhibitors + si-PTEN group (P < 0.05). [score:5]
The target site related to PTEN and miR-130a was determined via Target Scan software (http://www. [score:5]
Figure 6Note: (A) the mRNA expressions of miR-130 in HCAECs detected by qRT-PCR; B, the mRNA expressions of PTEN and the key molecules of PI3K-Akt-eNOS signaling pathway in HCAECs detected by qRT-PCR; HCAECs, Human coronary artery endothelial cells; HCY, homocysteine; PTEN, phosphatase and tensin homolog deleted on chromosome 10; PI3K, phosphatidylinositol 3-kinase; Akt: protein kinase (B) eNOS: endothelial nitric oxide synthase; compared with the blank and the NC groups, * P < 0.05; compared with the miR-130a inhibitors + si-PTEN group, [#] P < 0.05; compared with the miR-130a mimics + Wortmannin group, [&] P < 0.05). [score:4]
Note: (A) the mRNA expressions of miR-130 in HCAECs detected by qRT-PCR; B, the mRNA expressions of PTEN and the key molecules of PI3K-Akt-eNOS signaling pathway in HCAECs detected by qRT-PCR; HCAECs, Human coronary artery endothelial cells; HCY, homocysteine; PTEN, phosphatase and tensin homolog deleted on chromosome 10; PI3K, phosphatidylinositol 3-kinase; Akt: protein kinase (B) eNOS: endothelial nitric oxide synthase; compared with the blank and the NC groups, * P < 0.05; compared with the miR-130a inhibitors + si-PTEN group, [#] P < 0.05; compared with the miR-130a mimics + Wortmannin group, [&] P < 0.05). [score:4]
The mRNA expressions of PI3K were significantly higher in the miR-130a mimics and the si-PTEN groups while were significantly lower in the miR-130a inhibitors and the Wortmannin groups when compared with those in the blank and the NC groups (all P < 0.05). [score:4]
In conclusion, we provide compelling evidence that miR-130a could alleviate HCAECs injury and inflammatory responses by down -regulating PTEN and activating PI3K/Akt/eNOS signaling pathway, which can provide a new target for the treatment of CHD at the gene level. [score:4]
Compared with the miR-130a inhibitors + si-PTEN group, the concentration of NO was decreased in the miR-130a inhibitors group while was increased in the si-PTEN group (both P < 0.05). [score:4]
Compared with the blank and the NC groups, no significant difference was found for the protein expressions of PI3K, p-PI3K, p-Akt, and p-eNOS and the ratios of p-PI3K/PI3K, p-Akt/Akt and p-eNOS/eNOS in the miR-130a inhibitors + si-PTEN and the miR-130a mimics +Wortmannin groups (Figure 8 and Table 3). [score:4]
Figure 1MiR-130a directly target at PTEN(A) Target Scan used for predicting the 3′-UTR primers of miR-130a binding site with PTEN mRNA; (B) Dual luciferase reporter gene activity assay. [score:4]
Compared with the blank and the NC groups, the protein expressions of PI3K, p-PI3K, p-Akt, and p-eNOS and the ratios of p-PI3K/PI3K, p-Akt/Akt and p-eNOS/eNOS were higher in the miR-130a mimics and the si-PTEN group while were lower in the miR-130a inhibitors and the Wortmannin group (all P < 0.05). [score:4]
Compared with the control group (0 mmol/L), the relative expression of miR-130a in the cell supernatant of HCY -treated cells was decreased while the expression of PTEN mRNA was increased. [score:4]
MiR-130a can specifically inhibit the expression of UTR 3′ region of PTEN. [score:4]
Compared with the blank and the NC groups, the mRNA expressions of PTEN in the miR-130a mimics, the si-PTEN and the miR-130a mimics +Wortmannin groups were significantly increased while were significantly decreased in the miR-130a inhibitors group (all P < 0.05). [score:4]
Thus, we suspected that miR-130a may inhibit the PI3K/Akt/eNOS signaling pathway to cause HCAEC injury and HCAEC -mediated inflammatory responses. [score:3]
As shown in Figure 6, the mRNA expressions of miR-130a, PTEN, PI3K, AKT and eNOS in HCAECs of each group were detected by qRT-PCR. [score:3]
MiR-130a directly target at PTEN. [score:3]
Thus, for the following experiments treatment of HCAECs with 1.0 mmol/L HCY or PBS was used to further explore whether miR-130a promoted the function of the PI3K/Akt/eNOS signaling pathway in HCAEC injury and HCAEC -mediated inflammation via targeting PTEN (Figure 7 and Table 2). [score:3]
Subsequently, we conducted an experiment to investigate the effects of miR-130a on the PI3K/Akt/eNOS signaling pathway and concluded that the PI3K/Akt/eNOS signaling pathway was inhibited in HCAECs following HCY treatment after transfection with the miR-130a inhibitor. [score:3]
Effects of different doses of HCY on miR-130a and PTEN mRNA expressions in HCAECs. [score:3]
Effect of different doses (0, 0.1, 0.25, 0.5 and l. 0 mmol/L) of HCY on the expressions of miR-130a and PTEN mRNA in HCAEC cells detected by RT-qPCR. [score:3]
Diluted miR-130a inhibitor was used to form a complex with liposomes (total volume: 100 μl). [score:3]
Lipofectamine 2000 and microRNA-130a inhibitor were prepared in sterile Eppendorf tubes. [score:3]
No significant difference was found in the concentration of NO among the blank, NC, miR-130a inhibitors + si-PTEN and miR-130a mimics +Wortmannin groups (all P > 0.05). [score:3]
No significant difference was found in the concentrations of these inflammatory factors between the miR-130a inhibitors + si-PTEN and the miR-130a mimics +Wortmannin groups (all P > 0.05). [score:3]
Effects of different doses (0, 0.1, 0.25, 0.5 and l. 0 mmol/L) of HCY on the mRNA expressions of miR-130 and key molecules of PI3K-Akt-eNOS signaling pathway in HCAECs detected by qRT-PCR. [score:3]
No significant difference was found for the apoptotic rates in the miR-130a inhibitors + si-PTEN and the miR-130a mimics +Wortmannin groups in comparison to the blank and the NC groups (P > 0.05). [score:3]
Comparisons of the expressions of miR-130a, PTEN and the PI3K/Akt/eNOS signaling pathway-related proteins in HCAECs among eight groups. [score:3]
Compared with the miR-130a mimics +Wortmannin group, the protein expressions of PI3K, p-PI3K, p-Akt, and p-eNOS and the ratios of p-PI3K/PI3K, p-Akt/Akt and p-eNOS/eNOS were significantly increased in the miR-130a mimics group while decreased in the Wortmannin group (all P < 0.05). [score:2]
Compared with the blank and the NC groups, the concentrations of NO were increased in the miR-130a mimics and the si-PTEN groups while were decreased in the miR-130a inhibitors and the Wortmannin groups (all P < 0.05). [score:2]
Our study demonstrated that miR-130a activates PI3K/Akt/eNOS signaling pathway to reduce the HCAECs injury and inflammatory responses by down -regulating PTEN. [score:2]
However, due to the limitations of our funds and time of our study, mature miR-130a, pre-miR-130a and pri-miR-130a used for determining the functions of HCY on up -regulating miR-130a were not conducted. [score:2]
MiR-130a has recently been found to be involved in many critical processes in multiple types of human diseases, including ventricular arrhythmias, endothelial progenitor cell dysfunction and hepatic insulin sensitivity [12– 15]. [score:2]
The primers used in the reaction are shown in Table 5. U6 was regarded as an internal reference of miR-130a, and β-actin was regarded as an internal reference of PTEN, PI3K, AKT and eNOS mRNA expressions. [score:2]
Compared with the blank and the NC groups, the concentrations of IL-6, ICAM-1, IFN-γ, IL- 1β, TNF-α, IL-12 and IL-17 were decreased in the miR-130a mimics and the si-PTEN groups while were increased in the miR-130a inhibitors and the Wortmannin groups (all P < 0.05). [score:2]
In the present study, we focused on the mechanisms of miR-130a regulating PI3K/Akt/eNOS signaling pathway in HCAECs injury and inflammatory responses. [score:2]
Compared with the miR-130a mimics +Wortmannin group, the mRNA expression of PI3K was higher in the miR-130a mimics group while were lower in the Wortmannin group (both P < 0.05). [score:2]
showed that compared with the blank and the NC groups, the apoptotic rates were decreased in the miR-130a mimics and the si-PTEN groups while were increased in the miR-130a inhibitors and the Wortmannin groups (P < 0.05). [score:2]
The relationship between miR-130a and PTEN. [score:1]
The 293T cell was co -transfected with different plasmids (PTEN wild group, PTEN mutant group, PTEN wild/miR-130a group and PTEN mutant/miR-130a group). [score:1]
It has been proposed that miR-130a can promote the proliferation, migration and tube formation of vascular endothelial cells [11]. [score:1]
MTT assay revealed that compared with the blank and the NC groups, the cell activities at 24 h, 48 h and 72 h were higher in the miR-130a mimics and si-PTEN groups while were lower in the miR-130a inhibitors and the Wortmannin groups (all P < 0.05). [score:1]
MicroRNA-130a (miR-130a) is located at chromosome 11q12, close to the 11q13 area [10]. [score:1]
The apoptotic rate was lower in the miR-130a mimics group while was higher in the Wortmannin group than that in the miR-130a mimics +Wortmannin group (P < 0.05) (Figure 10). [score:1]
In order to prove that the change of luciferase activity was caused by binding site predicted by the miR-130a, we also designed the mutant and wild sequences which were loss the miR-130a binding site in PTEN 3′UTR, and inserted into reporter plasmid. [score:1]
The cell activity in the miR-130a mimics group was higher while in the Wortmannin group was lower than that in the miR-130a mimics +Wortmannin group (P < 0.05). [score:1]
In the present study, we aim to investigate the roles of miR-130a in HCAECs injury and inflammatory responses by targeting PTEN through the PI3K/Akt/eNOS signaling pathway. [score:1]
The concentrations of these inflammatory factors in the miR-130a mimics group were lower than those in the miR-130a mimics + Wortmannin group, and in the Wortmannin group were higher than those in the miR-130a mimics + Wortmannin group (all P < 0.05) (Table 4). [score:1]
Finally, we found that miR-130a may activate PI3K/Akt/eNOS signaling pathway following HCY treatment, and then successfully induce HCAEC injury and HCAEC -mediated inflammatory responses. [score:1]
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8
[+] score: 194
Other miRNAs from this paper: hsa-mir-211, hsa-mir-326
miRNA-130a has been found to be downregulated in a variety of carcinomas and exhibits tumor-suppressive activity [37- 39] while HOTAIR was demonstrated be an oncogene and upregulated in carcinomas [28- 30]. [score:9]
As miRNAs are known to mediate post-transcriptional control of gene expression by binding to the 3’-untranslated regions of protein coding genes, we suppose that the way that miR-130a promoted the downregulation of HOTAIR is somewhat similar to the miRNA -mediated silencing of protein-coding genes. [score:8]
Target sequences are listed in the Additional file 1. Hsa-miRNA-130a mimic/negative control mimic and hsa-miRNA-130a inhibitor/negative control inhibitor were purchased from Genechem, shanghai, China. [score:7]
Our data showed that while knockdown of HOTAIR inhibited the invasiveness and proliferation of gallbladder cancer cells, miRNA-130a inhibitor reversed the effects that knockdown of HOTAIR exerted. [score:7]
In contrast, ectopic expression of HOTAIR increased the expression level of HOTAIR (Figure  6A) while dramatically suppressed miRNA-130a (Figure  6B, C). [score:7]
Thus, we may hypothesize that HOTAIR may lead to the downregulation of miR-130a via increasing the methylation status of the promoter of miRNA-130a as Vrba et al. [35] demonstrated that the downregulation of miR-130a is linked to increased promoter methylation. [score:7]
On the other hand, miRNA-130a inhibitor upregulated HOTAIR level while miRNA-130a mimic repressed HOTAIR level. [score:6]
We demonstrated that knockdown of HOTAIR inhibited the invasion of gallbladder cancer cells while miRNA-130a inhibitor reversed the decrease in invasiveness (Figure  10A, B). [score:6]
indicated knockdown of HOTAIR suppressed cancer cells proliferation (S-phase fraction) in vitro while miRNA-130a inhibitor rescued the proliferation (Figure  10C, D). [score:6]
Knockdown of HOTAIR induced the upregulation of miRNA-130a. [score:5]
We also determined the expression levels of miRNA-130a in gallbladder cancer tissues from Figure  1. The miRNA-130a mRNA was markedly downregulated in gallbladder cancer tissues compared to adjacent normal tissues (p < 0.0001, Figure  9C). [score:5]
To explore the mechanism of the negative regulation of miRNA-130a by HOTAIR, we examined the effect of knockdown of HOTAIR on the expression level of mature miRNA-130a, pri-miRNA-130a and pre-miRNA-130a. [score:5]
Quantitative graphical representation of Apoptosis, G1, G2, S cell population (C) and a bar-graphical representation S-Phase Fraction cells in each group (D) transfected with si-NC, si-HOTAIR, miR-130a inhibitor or si-HOTAIR + miR-130a inhibitor. [score:5]
As demonstrated in Figure  8A, while HOTAIR siRNA induced a significant upregulation of mature miRNA-130a, it had no effect on pri-miRNA-130a or pre-miRNA-130a, implying this negative regulation might be through a post-transcriptional mechanism. [score:5]
Representative images (A) and the number of migratory cells (B) per high-power field transfected with si-NC, si-HOTAIR, miR-130a inhibitor or si-HOTAIR + miR-130a inhibitor. [score:5]
Furthermore, miRNA-130a inhibitor increased the expression of HOTAIR (Figure  7B). [score:5]
In this study, we present evidence that HOTAIR is a direct target of c-Myc and exhibits oncogenic activity partly through negative regulation of miRNA-130a. [score:5]
HOTAIR expression was negatively correlated with miRNA-130a in gallbladder cancer tissues (r = -0.6398, p < 0.0001, Figure  9D), providing evidence to the reciprocal negative regulation of HOTAIR and miRNA-130a. [score:4]
GBC-SD cells were transfected with vector, miR-130a mimic (A) or miR-130a inhibitor (B), and total RNA was isolated for qRT-PCR 24 h after transfection. [score:3]
HOTAIR expression is positively correlated with c-Myc and negatively correlated with miRNA-130a in gallbladder cancer tissues. [score:3]
Figure 9 Expression of HOTAIR, c-Myc and miRNA-130a mRNA levels in human gallbladder cancer samples. [score:3]
The expression levels of HOTAIR, c-Myc and miRNA-130a were examined in 65 matched pairs of gallbladder cancer tissues. [score:3]
To determine whether this suppression is through the potential interaction at the putative miRNA-130a -binding site, we generated a HOTAIR mutant (Figure  6D). [score:3]
However, luciferase expression in cells transfected with HOTAIR mutant and the miR-130a mimics was comparable to that of control cells (Figure  7D). [score:3]
The si-HOTAIR-blocked migratory ability of GBC-SD cells was rescued by miR-130a inhibitor. [score:3]
In support of this notion, we demonstrate that HOTAIR -mediated oncogenic activity is at least partly through suppression of miRNA-130a. [score:3]
miRNA-130a mRNA expression was analyzed by real-time PCR and normalized to GADPH. [score:3]
To further confirm that the miR-130a target site is functional, luciferase reporter constructs were generated (Figure  7C). [score:3]
Our data also reveal that HOTAIR negatively regulates miRNA-130a and the oncogenic activity of HOTAIR is, at least in part, through the negative regulation of miRNA-130a, which may function as a part of the “competitive endogenous RNAs (ceRNA)” network [22]. [score:3]
Ectopic expression of HOTAIR reduced the miRNA-130a level and the miRNA-130a -binding site is vital for the HOTAIR -mediated repression. [score:3]
Figure 6 Identification of miR-130a as a target of HOTAIR. [score:3]
Si-HOTAIR induced a reduction of S-Phase Fraction cells in GBC-SD cells, which can be rescued by miR-130a inhibitor. [score:3]
This study provides experimental evidence to the existence of the ceRNA regulatory network [22] where HOTAIR and miRNA-130a negatively regulate each other. [score:3]
These results may imply that the oncogenic activity of HOTAIR is partly through negative regulation of miRNA-130a. [score:2]
The data revealed that luciferase expression was obviously reduced in cells transfected with HOTAIR and miR-130a mimics compared with that in cells transfected with HOTAIR and negative control. [score:2]
Figure 8 The mechanism of the regulation of miR-130a by HOTAIR. [score:2]
Our data showed that this binding site is vital for the regulation of miRNA-130a by HOTAIR. [score:2]
This mutant HOTAIR clone revealed no significant suppression of miRNA-130a compared with wide-type of HOTAIR (Figure  6B, C). [score:2]
We then focused on miRNA-130a (Figure  5A), which is of the greatest fold-change in response to HOTAIR knockdown. [score:2]
To determine whether miRNA-130a is able to negatively regulate HOTAIR, we also transfected miRNA-130a mimic into GBC-SD cells. [score:2]
HOTAIR’s oncogenic activity is in part through negative regulation of miRNA-130a. [score:2]
The primer sequences were listed in the Additional file 1. Expression plasmids for HOTAIR, c-Myc or corresponding mutants of HOTAIR by mutating the has-miRNA-130a seed region binding site (seed sequence binding fragment 5’-GACTTTGCACT -3’ changed to 5’-TTGTAACGTGA-3’) were created using PCR amplification with human genomic DNA as templates. [score:2]
Finally, we demonstrate that the oncogenic activity of HOTAIR is in part through its negative regulation of miRNA-130a. [score:2]
Figure 7 Reciprocal negative regulation of miR-130a and HOTAIR. [score:2]
The correlation coefficient, R = -0.6398, p <0.0001, indicates there is a strongly negative relationship between miRNA-130a and HOTAIR. [score:1]
We found that HOTAIR and miRNA-130a bind to the same RISC complex. [score:1]
HOTAIR siRNAs significantly reduced the endogenous HOTAIR (Figure  5B); at the same time, HOTAIR siRNA increased the miRNA-130a level (Figure  5C, D). [score:1]
Our study further demonstrated that the reciprocial repression of HOTAIR and miRNA-130a is likely through the pathway involving RISC complex. [score:1]
In addition, a negative correlation was observed between HOTAIR and miRNA-130a in gallbladder cancer tissues, providing supporting evidence to such a feedback loop. [score:1]
Oligonucleotides complementary to mature miR-130a (5’-AGCAAAAATGTGCTAGTGCCAAA-3’) were end-labeled with T4 Kinase (Invitrogen) and used as probes. [score:1]
We then then studied that biological function of HOTAIR and miRNA-130a in gallbladder cancer cells. [score:1]
What’s more, we detected miRNA-130a in the same pellet (Figure  8C). [score:1]
WT HOTAIR or HOTAIR mutant devoid of the miR-130a binding site was cloned downstream of Renilla luciferase gene and transfected into 293 T cells together with specific miR-130a mimics or the negative control mimic. [score:1]
To determine whether HOTAIR is associated with the RNA -induced silencing complex (RISC) complex, we performed using synthesized biotin-labeled HOTAIR as a probe and then detected Ago 2 from the pellet by western or detected miRNA-130a by quantitative RT-PCR (qRT-PCR). [score:1]
Moreover, a negative correlation between HOTAIR and miRNA-130a was observed in gallbladder cancer tissues. [score:1]
Reciprocal repression of miRNA-130a and HOTAIR. [score:1]
To determine whether miRNA-130a and HOTAIR are in the same RISC complex, we performed RNA pull-down experiments using HOTAIR probe and then examined Ago2 and miRNA-130a simultaneously as described previously [16, 17]. [score:1]
Together, these results suggest that HOTAIR is a c-Myc-activated driver of malignancy, which acts in part through repression of miRNA-130a. [score:1]
Gain and loss of function approaches were employed to investigate the expression changes of HOTAIR or miRNA-130a. [score:1]
Thus, these results indicate that both HOTAIR and miRNA-130a are probably in the same Ago2 complex. [score:1]
As shown in Figure  7A, miRNA-130a mimic reduced the HOTAIR level by approximately 64%. [score:1]
We predicted that HOTAIR harbors a miRNA-130a binding site. [score:1]
These data demonstrates that the binding sites are vital for the reciprocal repression of HOTAIR and miRNA-130a. [score:1]
HOTAIR and miRNA-130a may form a reciprocal repression feedback loop. [score:1]
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9
[+] score: 166
As shown in Fig 4, miR-130a inhibition increased PTEN protein levels and attenuated the expressio of MDR1 mRNA and P-gp (P<0.05),whereas miR-130a overexpression resulted in the up-regulation of MDR1 mRNA and P-gp expression in A2780 and A2780/DDP cells(P<0.05). [score:12]
The expression of PTEN protein was significantly elevated When cells were treated with miR-130a-I, the expression of P-gp were upregulated by miR-130-M and downregulated by miR-130a-I. (C1,C2): PTEN and MDR1 mRNA in A2780/DDP cells after transfection. [score:11]
Interestingly, We found that miR-130a didn’t regulate PTEN mRNA expression likewise PTEN protein, suggesting that miR-130a may regulate the PTEN gene transcription at post-translational level by incomplete bind to the 3'-untranslated region (3'-UTR) of the PTEN mRNA. [score:9]
Among them, one down-regulated miRNA (miR-146a) and three up-regulated miRNAs(miR-130a, -374a,-182) were selected for further study, and their expression were validated consistently with miRNA array using qRT-PCR. [score:9]
The MDR1 mRNA level was upregulated by the miR-130a mimics and downregulated by the miR-130a inhibitor(P<0.01). [score:9]
Up-regulation of miR-130a could affect the doxorubicin resistance in breast cancer[20], and miR-130a induced the resistance of liver cancer cell to cisplatin by downregulation of tumor suppressor gene RUNX3[21]. [score:9]
The data of microarray revealed that in A2780/DDP the expression of miR-146a was extremely low, and miR-130a, -374a, -182 was up-regulated. [score:6]
We concluded that inhibiting the expression of miR-130a resulted in down -regulating of MDR1 mRNA and P-gp. [score:6]
In addition, our previous study[15] had found that miR-130a was upregulated in S KOV3/DDP compared with S KOV3, and miR-130a inhibition could overcome the cisplatin resistance by regulating the MDR1/P-gp pathway. [score:6]
In the transfection experiment, overexpression of miR-130a and miR-374a were found to decrease the sensitivity of A2780 and A2780/DDP cells to cisplatin, and down -regulating the miR-130a and miR-374a expression exerted the opposite effect. [score:6]
Cells inhibition by cisplatin following pre-treatment with miR-130a, -374a mimics or inhibitors. [score:5]
Inhibiting the expression of miR-130a and miR-374a might be a novel approach for overcoming drug resistance in ovarian cancer. [score:5]
In our previous study[15], miR-130a was overexpressed in S KOV [3]/DDP cells, and inhibition of miR-130a could partially restore cisplatin sensitivity, which was consistant with above study. [score:5]
The results of RT-PCR and western blot showed that miR-130a could positively regulate the mRNA and protein expression of MDR1 and negatively regulate the PTEN protein, which may be one of the mechanisms of miR-130a’s role in chemoresistance. [score:5]
The expression of PTEN mRNA didn’t change with the treatment of miR-130a inhibitor and mimics in both cell lines(P>0.05). [score:5]
We also found that miR-130a negatively regulated the expression of PTEN protein. [score:4]
Therefore, we considered that over -expression of miR-130a and miR-374a might contribute to the development and regulation of cisplatin resistance in ovarian cancer cells. [score:4]
miR-130a and miR-374a mimics or inhibitors regulate cisplatin sensitivity in A2780 and A2780/DDP. [score:4]
The role of miR-130a in drug resistance was achieved at least partially by regulating the expression of P-gp and PTEN protein. [score:4]
However, the role of miRNAs prensents cell specificity, so the expression of miR-130a or other miRNAs and their roles in other ovarian cancer cell lines are needed to further study. [score:3]
Moreover, transfection with miR-130a and miR-374a inhibitors enhanced the cytotoxic effect of cisplatin. [score:3]
The expression of miR-130a, -374a and miR-182 was 4.8, 2.08 and 1.28 folds higher than that in A2780 cells (** p<0.05, * p<0.05). [score:3]
PTEN may be a target gene of miR-130a, however, it needs the validation of dual luciferase reports. [score:3]
The results showed that the A2780 cells transfected with miR-374a and miR-130a mimics had a significantly higher survival than the control group under the treatment of 0.8, 3.2 ug/ml cispaltin, but same phenomenon was not observed for miR-182 mimics and miR-146a inhibitor. [score:3]
In the transfection experiments, we found alteration of miR-130a and miR-374a expression could change the degree of cisplatin resistance in A2780 and A2780/DDP. [score:3]
We further transfected with miR-374a and miR-130a inhibitors into A2780/DDP cells to explore whether they can partially reverse the cisplatin resistance. [score:3]
These results suggest that miR-130a and miR-374a could be promising as novel therapeutic targets for overcoming drug resistance. [score:3]
MiR-130a regulate the expression of MDR1 and PTEN in A2780s and A2780/DDP cells. [score:3]
In addition, miR-130a’s role in cisplatin resistance of A2780 cells and whether miR-146a, -374a, -182 could regulate drug resistance have not yet reported, so we choose these four miRNAs for further study. [score:2]
However, A2780 and A2780/DDP cells transfected with miR-130a -inhibitor didn’t exert higher cell activity inhibition compared with the control groups under the treatment of low-dose cisplatin (0.2ug/ml and 2ug/ml respectively), we calculated the reason of this phenomenon is that PTEN -mediated cell apoptosis partly rely on the cell damage by cisplatin and they have a synergistic effect. [score:2]
As a result, we also performed RT-PCR and western blot to find the mechanism of miR-130a regulatory effect on drug resistance. [score:2]
The regulatory effect of miR-130a on A2780/DDP cells was similar to that of A2780 cells. [score:2]
Several researches have shown that miR-130a acted as chemoresistant regulator. [score:2]
As shown in Fig 2B, miR-374a and miR-130a inhibitor significantly enhanced the cytotoxicity of cisplatin treatment compared with that of the control (p<0.05). [score:2]
The effect of miR-130a was similar to that of A2780s cells. [score:1]
0128886.g002 Fig 2(A) The A2780 cells after transfection with miR-130a -mimic and miR-374a -mimic showed a increased ratio of surviving cells under the treatment of 0.8, 3.2 ug/ml cispaltin (* p<0.05). [score:1]
Our previous study also found miR-130a was related to cisplatin-resistance in S KOV3 cells. [score:1]
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[+] score: 140
Intringuingly, out of the 12 validated miRNA hits, five (miR-148a, miR-17-5p, miR-25, miR-130a, and let-7a) were significantly downregulated by HCV, while others were also suppressed, but to a lesser extent (Fig.   2e). [score:6]
Interestingly, HCV seems to evade miR-130a -mediated inhibition by down -regulating its expression, demonstrated in PHHs and Huh7.5.1 cells (Fig.   6d). [score:6]
Five miRNAs targeted the replication stage only, as their overexpression significantly enhanced (miR-151-5p) or diminished (miR-130a, miR-196a, miR-148a, and miR-30a-5p) HCV RNA replication but not IRES -mediated translation in the replicon assays (Fig.   3c). [score:6]
We conducted using luciferase reporters and demonstrated that miR-130 mimic had limited effect on their 3′-UTR activities, except ROCK2 showed moderate inhibition (Supplementary Fig.   14c), suggesting that these genes probably are not targets of miR-130. [score:5]
a, b miR-130a mimic or inhibitor transfection in Huh7.5.1 cells inhibits or enhances HCV infection, respectively. [score:5]
Transfecting miR-130b mimic in cells markedly decreased both the 3′-UTR activities and mRNA levels of the six miR-130a -targeted genes, indicating that miR-130b targets the same panel of HCV host dependencies as miR-130a for its antiviral functions (Supplementary Fig.   13c–e). [score:5]
Transcriptome analysis of miR-130a mimic overexpressing cells revealed that multiple cell signaling pathways closely related to LD biogenesis were significantly inhibited (Fig.   6j). [score:5]
f, g miR-130a mimic transfection inhibits 3′-UTR activities (f) and mRNA levels (g) of various predicted cellular targets in Huh7.5.1 cells. [score:5]
Notably, the inhibitors of less-abundant family members (e. g., miR-130b) exerted less effects than that of the more highly expressed (i. e., miR-130a). [score:5]
Interestingly, miR-25, miR-130a/b, and let-7a—three most relevant antiviral miRNAs physiologically interacting with HCV—are downregulated by the virus, demonstrated in both cultured cells and liver tissues of CHC patients. [score:4]
j Bioinformatics -based pathway analysis was conducted for miR-130a downregulated genes (Supplementary Data  7) using IPA. [score:4]
Similarly, the lentiviral vector -based miR-130a overexpression inhibited HCV infection in both part-one and part-two assays (Supplementary Fig.   11d, e). [score:4]
In our primary screen, two major miR-130 miRNAs, miR-130a-3p and miR-130b-3p (denominated as miR-130a/b hereafter), and another family member, miR-301a, were shown to effectively inhibit HCV infection (Supplementary Fig.   11a). [score:3]
However, these genes were not transcriptionally regulated by miR-130a as shown in the microarray analysis (Supplementary Data  7) and confirmatory qPCR gene expression assay (Supplementary Fig.   14b). [score:3]
Transfection of miR-130a synthetic mimic in Huh7.5.1 cells significantly decreased core protein and HCV RNA expression (Fig.   6a–c; Supplementary Fig.   11c). [score:3]
Transfection of miR-130a inhibitor considerably enhanced core protein production in part two of the screen, whereas a modest increase was seen in part one (Fig.   6a). [score:3]
These include miR-27 and miR-130a/b, which enhance IFN production and the expression of various interferon-stimulated genes (ISGs) in hepatocytes 30, 35, 45. [score:3]
h, i Representative images and quantitative analyses of LD contents in Huh7.5.1 cells transfected with control or miR-130a inhibitor (h) or mimic (i). [score:3]
miR-130a inhibition also elevated HCV RNA levels; with a more profound effect exerted on the level of secreted viral RNA (Fig.   6b). [score:3]
Therefore, DDX6, E2F2, HCCS, INTS6, LDLR, and NPAT likely mediate miR-130’s inhibitory effect on HCV replication (Supplementary Fig.   12f). [score:3]
Of note, hepatic miR-130a expression levels were unrelated to the extent of fibrosis (Supplementary Fig.   11f). [score:3]
miR-130 miRNAs suppress HCV replication and assembly. [score:3]
c Transfection efficiency of miR-130a mimic overexpression in Huh7.5.1 cells. [score:3]
This is likely due to the continued function of endogenous miR-130a when the less abundant miR-130b is inhibited. [score:3]
d HCV infection decreases miR-130a expression in Huh7.5.1 cells and PHH. [score:3]
In contrast, blocking miR-130a functions with its hairpin inhibitor markedly enhanced HCV production (Fig.   6a, b). [score:3]
All six genes contain at least one miR-130 seed match site in their 3′-UTRs (Supplementary Fig.   12c), the activities of which were drastically inhibited by miR-130a transfection (Fig.   6f). [score:3]
We demonstrated a similar role of miR-130a as transfection of its hairpin inhibitor markedly induced LD contents in Huh7.5.1 cells (Fig.   6h), likely contributing to its role in enhancing HCV assembly. [score:3]
These results confirmed that miR-130a represses the expression of the six host factors. [score:3]
After 24 h, the media was replaced with Transduction Medium (DMEM (4.5 g/L glucose, Sodium Pyruvate, 25 mM HEPES, no L-Glut) with 10% FBS, and Polybrene (AmericanBio) at a concentration of 4 µg/mL] combined with either the active control (SMARTvector Non -targeting hCMV-TurboGFP Control), miR-130a (shMIMIC Human Lentiviral microRNA has-miR-130a-3p hCMV-TurboGFP), miR-25 (shMIMIC Human Lentiviral microRNA has-miR-25-3p hCMV-TurboGFP), or let-7a (shMIMIC Human Lentiviral microRNA has-let-7a-5p hCMV-TurboGFP) (GE Dharmacon). [score:3]
Noticeably, bioinformatics -based target prediction revealed six other essential HCV host factors—OSBP, PI4KA, RAB10, RABEPK, ROCK2, and VAMP1 that bear miR-130a/b match sites in their 3′-UTRs (Supplementary Fig.   14a). [score:3]
The reliance of HCV infection on these miR-130 targets was validated by siRNA -mediated loss-of-function assays. [score:2]
Viral life cycle assays indicate that miR-130a, the family member with the highest expression level in hepatocytes (Supplementary Fig.   11b), preferentially interferes with HCV RNA replication (Fig.   3f). [score:2]
Li S MicroRNA-130a inhibits HCV replication by restoring the innate immune responseJ. [score:2]
We uncovered multiple miRNAs as regulators of HCV infection, including the miR-25, let-7, and miR-130 families. [score:2]
Among them, three are proviral miRNAs (miR-122, miR-151-5p, and miR-17-5p), and nine others, including let-7a, let-7b, miR-130a, miR-148a, miR-181a, miR-196a, miR-30a-5p, miR-99b, and miR-25, are antiviral factors (Fig.   2c). [score:1]
let-7a, miR-130a, miR-130b, and miR-25 expression levels were determined by qPCR using TaqMan Universal PCR Master Mix (Applied Biosystems) and specific miRNA primers and probes (TaqMan MicroRNA Assays, Applied Biosystems). [score:1]
These include SUV420H1 for miR-25; PPIA, IQCB1, IGF2BP1, and CLDN1 for let-7a; and DDX6, NPAT, LDLR, HCCS, and INTS6 for miR-130a. [score:1]
As such, miR-130a alters hepatocellular lipogenic pathways to impede HCV assembly (Supplementary Fig.   12 f). [score:1]
We further dissected the functions and underlying mechanisms of three physiologically relevant miRNA families (miR-25, let-7, and miR-130) in modulating HCV infection. [score:1]
These results confirmed a crucial role of miR-130a in restricting HCV infection. [score:1]
The mRNA levels of these genes were also markedly reduced in miR-130a -transfected cells (Fig.   6g). [score:1]
We also investigated the antiviral effect of miR-130b, though it is expressed at a lower level in hepatocytes than miR-130a (Supplementary Fig.   11b). [score:1]
In contrast, treatment of cells with miR-130a mimic drastically reduced oleic acid-triggered LD formation (Fig.   6i). [score:1]
Next we dissected the functions and mechanisms of three miRNAs: miR-25, let-7a, and miR-130a in modulating HCV infection. [score:1]
We noted that HCV assembly/secretion was also affected in miR-130a-sequestered cells. [score:1]
Huh7.5.1 cells were transfected with miRNA mimic control or let-7a, miR-130a, or miR-25 mimic at 25 nM for 72 h, in triplicate. [score:1]
Fig. 6Identification of miR-130a that restricts HCV RNA replication and assembly. [score:1]
e Comparison of hepatic miR-130a abundance between liver samples of CHC patients and those of healthy controls. [score:1]
We elucidated the mechanism by which miR-130a modulates HCV assembly/secretion. [score:1]
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[+] score: 124
Interestingly, 7 of the 12 miRNAs that were up-regulated in the presence of IFN-α (miR-30b,miR-30c, miR-130a, miR-192, miR-301, miR-324-5p and miR-565) were also down-regulated in HCV -infected Huh7.5 cells. [score:7]
Seven miRNAs (miR-30b, miR-30c, miR-130a, miR-192, miR-301, miR-324-5p, and miR-565) were down-regulated in HCV-infected Huh7.5 cells (p<0.05) and subsequently up-regulated following interferon-α treatment (p<0.01). [score:7]
Inhibition of miR-30c expression significantly enhanced HCV replication (951.5 HCV RNA copies, p value = 0.029) while miR-130a inhibition decreased HCV RNA compared to the HCV infected Huh7.5 control (352 mean HCV RNA copies, p value = 0.018). [score:6]
Our data suggests that, in addition to possible antitumor effects, treatment of HCV-infected Huh7.5 cells with IFN-α upregulates miR-130a/301 thereby reducing c-Met expression and HCV pathogenesis. [score:6]
MiR-324-5p (FC = 6.26, p = 0.003) and miR-489 (FC = 9.34, p = 0.006) exhibited the greatest degree of up-regulation in the presence of IFN-α while miR-30c and miR-130a demonstrated the greatest difference in expression between HCV-infected Huh7.5 cells treated with or without IFN-α (Fig. 3C). [score:6]
Of the 7 down-regulated miRNAs, miR-324-5p and miR-130a exhibited the greatest reduction in expression at a fold change (FC) of 3.50 (p = 0.0246) and 3.48 (p = 0.0110) respectively (Fig. 1C). [score:6]
In this regard, a recent study suggested that miR-130 mediates suppression of HCV replication by inducing the expression of Interferon stimulating gene (ISG), IFITM3 [35]. [score:5]
To test the association between selected miRNA-130a/301-mRNAs found using DAVID, real-time quantitative RTPCR was performed on 7 highly predicted mRNAs of gene targets from the endocytosis pathway and 7 highly predicted gene targets from the TGF-β signaling pathway (Table 1) in HCV-infected Huh7.5 cells without IFN-α or following a 24-hour treatment with IFN-α. [score:5]
Predicted mRNA Targets Correlate with miRNA-130a/301 Expression during HCV Infection and IFN Treatment in vitro. [score:5]
The GOMir tool JTarget, using five major miRNA-mRNA prediction databases, identified a list of mRNA targets for miR-30, miR-130a, miR-192, miR-301 and miR-324-5p [21]. [score:5]
The majority of mRNA targets correlated with miR-130a/301 and involved in TGF-β signaling exhibited expression levels that were reduced in the presence of HCV infection and subsequently increased following IFN-α treatment with the exception of SMAD5 and Tumor Necrosis Factor (TNF). [score:5]
Expression of mRNA targets of miR-130a/301 in HCV-infected Huh7.5 treated with IFN-α. [score:5]
Our data suggest that the miR-30(a–d) cluster and miR130a/301are significantly associated with gene targets found in pathways that involve HCV entry and replication, and thus, may play a role in the pathogenesis of chronic liver disease. [score:5]
The top seven highly predicted mRNAs of gene targets for miR-130a/301 found in the endocytosis pathway (A) and TGF-β signaling pathways (B) were tested for expression using real-time quantitative RT-PCR and HCV-infected Huh7.5 cells without IFN-α (HCV effect) and with IFN-α (HCV+ IFN effect). [score:5]
We found the reverse HCV effect following the inhibition of miR-130a/301 expression. [score:5]
0055733.g004 Figure 4 The top seven highly predicted mRNAs of gene targets for miR-130a/301 found in the endocytosis pathway (A) and TGF-β signaling pathways (B) were tested for expression using real-time quantitative RT-PCR and HCV-infected Huh7.5 cells without IFN-α (HCV effect) and with IFN-α (HCV+ IFN effect). [score:5]
Predicted mRNA Targets Correlate with miRNA-130a/301 Expression during HCV Infection and IFN Treatment in vitro Although bioinformatic analyses of miRNA-mRNA correlated pairs provides a framework to predict miRNA interactions in a cellular environment following HCV infection, the functional importance of the predicted miRNA/mRNA interaction needs to be validated. [score:5]
There is a significant probability that the predicted seed match of miR130a/301 binds to the 3′ UTR of MET (Table 2), but there is no direct evidence that the differential expression of miR-130a/301 results in an anti-viral effect. [score:4]
We found that miRNA 30(a–d) and miR-130a/301 share mRNA targets in biological pathways that interact directly with viral entry and propagation. [score:4]
The DAVID Pathway analysis tool applied to the same data sets revealed targeted bio-pathways for the miR-30 cluster (miR-30a, miR-30b, miR-30c and miR-30d) and miR-130a/301 cluster (Table 1). [score:3]
Location of putative miR-130a binding sites in the 3′ UTR of target mRNAs. [score:3]
The miR-30(a-d) cluster and miR-130a/301 and their putative mRNA targets were predicted to be associated with cellular pathways that involve Hepatitis C virus entry, propagation and host response to viral infection. [score:3]
The mRNAs of targeted genes for miR-130a/301 were found in the endocytosis and TGF-β signaling pathways (Fig. S4, Fig. S5). [score:3]
Predicted binding of miR-130a/301 seed sequences to the 3′UTR of SMAD4 and SMAD5 was highly probable (Table 3) but not at the level of other gene targets identified in the TGF-β signaling pathway. [score:3]
Figure S5 MiR-130a -associated gene targets in the Endocytosis pathway. [score:2]
Anti-miRs specific for 5 miRNAs down regulated upon HCV infection (miR-30b, miR-30c, miR-130a, miR-192, and miR-324-5p) were tested against a mock -transfected HCV [+] Huh7.5 cell control (Fig. 2). [score:2]
Figure S4 MiR-130a -associated gene targets in the TGF-β signaling pathway. [score:2]
A Mann-Whitney test of multiple comparisons confirmed a significant increase in HCV RNA for Ant-miR-30c and significant decrease in HCV RNA for miR-130a. [score:1]
Further characterization of mRNAs of gene targets in the endocytosis pathway may reveal the mechanism(s) associated with reduced HCV replication in infected Huh7.5 cells in the absence of miR-130a/301. [score:1]
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[+] score: 73
Other miRNAs from this paper: hsa-mir-130b, hsa-mir-454
In addition, miR-130a-3p inhibitors nullified the inhibitory effect of HOXD-AS1 on the expression of SOX4 (Fig.   5f). [score:7]
To further explore the ceRNA role of HOXD-AS1, the expression levels of SOX4 after overexpression or knockdown of miR-130a-3p were examined. [score:6]
As shown in Fig.   5f, overexpression of miR-130a-3p could reduce the levels of SOX4, which rescued by the overexpression of HOXD-AS1. [score:5]
Overexpression of HOXD-AS1 competitively bound to miR-130a-3p that prevented SOX4 from miRNA -mediated degradation, thus activated the expression of EZH2 and MMP2 and facilitated HCC metastasis. [score:5]
Furthermore, we detected competitive binding activities of HOXD-AS1 and SOX4 to miR-130a-3p in SNU449 cells with HOXD-AS1 overexpression and Huh7 cells with HOXD-AS1 knockdown. [score:4]
HOXD-AS1 functions as a ceRNA that competitively binds to miR-130a-3p, then upregulates SOX4 and promotes HCC cell metastasis. [score:4]
Right: Protein level of SOX4 after transfection of miR-130a-3p inhibitors in Huh7 cells with HOXD-AS1 knockdown. [score:4]
In addition, previous study reported that miR-130a-3p could suppress cell migration and invasion in HCC cells [31]. [score:3]
f Left: Protein level of SOX4 after transfection of miR-130a-3p mimics in SNU449 cells with HOXD-AS1 overexpression. [score:3]
We found that reporter with wild type binding sites of HOXD-AS1 or SOX4 showed a markedly lower luciferase activity in HEK-293 T cells with overexpression of miR-130a-3p, however, we did not observe variations of luciferase activity in reporter with the mutated binding sites (Fig.   5c). [score:3]
showed that overexpression of HOXD-AS1 in SNU449 cells led to the decreased enrichment of SOX4 transcripts on miR-130a-3p. [score:3]
We found that miR-130a-3p suppressed endogenous SOX4 in HCC cells (Fig.   5d). [score:3]
These results demonstrate that HOXD-AS1 regulates SOX4 partly in miR-130a-3p dependent manner by sharing miRNAs response elements with SOX4. [score:2]
However, HOXD-AS1 knockdown in Huh7 cells caused a significant increase in the recruitment of SOX4 to miR-130a-3p (Additional file 11: Figure S7A-B). [score:2]
To confirm HOXD-AS1 and SOX4 were regulated by miR-130a-3p, we constructed luciferase reporters containing wild type (WT) and mutated (MUT) putative binding sites of HOXD-AS1 or SOX4 transcripts, respectively (Additional file 10: Figure S6B-C). [score:2]
MiR-130a-3p mimics, inhibitors and corresponding negative control (NC) were synthesized by Ribobio (Guangzhou, China). [score:2]
These results suggest that miR-130a-3p may be a critical regulatory miRNA for HOXD-AS1 and SOX4. [score:2]
Additionally, to validate the direct binding ability of miR-130a-3p on HOXD-AS1 and SOX4, we performed biotin-coupled miRNA pull down to capture HOXD-AS1 and SOX4 using streptavidin-coated beads from cells transfected with 3’end- biotinylated miR-130a-3p (Bi-has-miR-130a-3p). [score:2]
The level of HOXD-AS1 or SOX4 in the pull down of Biotin-miR-130a-3p or negative control was quantified by real-time PCR. [score:1]
d Protein levels of SOX4 following transfection of miR-130a-3p mimics or NC into Huh-7 and SMMC-7721 cells. [score:1]
According to the prediction, miR-130a-3p, miR130b-3p, and miR454-3p have the same putative binding sites mapped to HOXD-AS1 and SOX4. [score:1]
c Firefly luciferase activity normalized to Renilla luciferase activity in HEK-293 T cells co -transfected with luciferase reporters with wild type or mutant transcripts of HOXD-AS1 or SOX4 along with miR-130a-3p mimics or negative control (NC). [score:1]
Putative binding sites of HOXD-AS1 and SOX4 with miR-130a-3p. [score:1]
The results showed that only miR-130a-3p was greatly reduced (Additional file 10: Figure S6A). [score:1]
In this study, we revealed that HOXD-AS1 could function as a ceRNA that sponge miRNA130a-3p to protect SOX4 against degradation. [score:1]
Competitive binding activities of HOXD-AS1 and SOX4 to miR-130a-3p. [score:1]
e mRNA level of HOXD-AS1 was detected by biotin-coupled miR-130a-3p pull-down in Huh7 and SMMC-7721 cells. [score:1]
Biotin was attached to the 3’-end of miR-130a-3p or negative control mimics. [score:1]
1 × 10 [6] HCC cells were transfected with 100 pmol Bi-miR-130a-3p, or negative control using Lipofectamine 2000 according to the manufacturer’s protocol. [score:1]
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[+] score: 49
MiR-27b mimic, miR-142 mimic, miR-206 mimic, miR-21 mimic, miR-130a mimic, mimic negative control, miR-27b inhibitor, miR-142 inhibitor, miR-206 inhibitor, miR-21 inhibitor, miR-130a inhibitor, and inhibitor negative control were obtained from RiboBio (Guangzhou, China). [score:13]
To validate whether miR-27b, miR-206, miR-21, and miR-130a regulate CYP3A4 and miR-27b and miR-142 regulate CYP3A5 by directly targeting binding sites, wild-type and mutant versions of CYP3A4 3′-UTR and CYP3A5 3′-UTR were constructed and cloned downstream of a luciferase reporter gene. [score:6]
PPARα was reported to regulate the expression of CYP3A4 36 and was found to be regulated by miR-21, miR-27 and miR-130a 37 38. [score:5]
The expression levels of four related miRNAs, namely, miR-27b, miR-21, miR-130a, and miR-142, were significantly negatively associated with CYP3A4 mRNA expression level. [score:5]
Multiple binding sites were mutated in has-miR-130a because it has three predicted targets. [score:3]
However, the luciferase activities of neither the pRB/CYP3A4 wild-type nor the mutant plasmid were affected by miR-21 and miR-130a (Supplementary Fig. S2a,b), indicating that miR-21 and miR-130a did not target the predicted binding sites in the CYP3A4 3′-UTR. [score:3]
Three miRNAs predicted to target the CYP3A5 sequence, namely, miR-21, miR-130a, and miR-142, were marginally negatively associated with CYP3A5 mRNA level in 55 human liver tissues. [score:3]
The relative level of CYP3A4 mRNA was significantly decreased by mimics of miR-27b, miR-142, miR-206 and miR-130a, compared with negative controls, while the level of CYP3A4 mRNA was increased by inhibitors of miR-27b and miR-142. [score:2]
To investigate the effects of miR-27b, miR-206, miR-21, miR-130a and miR-142 on regulation of CYP3A activity, 75 nM mimic or 100 nM inhibitor of miRNA or control was transfected into human primary hepatocytes using Lipofectamine 3000 (Invitrogen Life Technologies, USA). [score:2]
MiR-27b, miR-206, and miR-130a were significantly negatively correlated with the formation rates of OAT (r = −0.43, P = 0.001, FDR = 0.013; r = −0.36, P = 0.007, FDR= 0.030; r = −0.36, P = 0.007, FDR = 0.030, respectively). [score:1]
MiR-27b, miR-130a, and miR-27a were also negatively correlated with CYP3A activity in human liver tissues. [score:1]
MiR-142, miR-130a, and miR-21 were marginally negatively associated with CYP3A5 mRNAs. [score:1]
MiR-27b, miR-206, miR-21, miR-27a, and miR-130a were significantly negatively correlated with the formation rates of PAT (r = −0.46, P = 0.001; FDR= 0.013; r =−0.39, P = 0.003, FDR = 0.013; r = −0.35, P = 0.010, FDR= 0.033; r = −0.33, P = 0.014, FDR = 0.036; r = −0.39, P = 0.003, FDR = 0.013, respectively, Supplementary Table S2). [score:1]
Among the 13 miRNAs tested, miR-27b, miR-130a, miR-21, and miR-142 were significantly negatively associated with CYP3A4 mRNA in the human liver. [score:1]
Therefore, a total of 13miRNAs, namely miR-21-5p, miR-27a-3p, miR-27b-3p, miR-103a-3p, miR-106a-5p, miR-107, miR-126-5p, miR-130a-3p, miR-142-5p, miR-206, miR-371b-5p, miR-491-3p, and miR-1260b, were selected. [score:1]
Human CYP3A4 3′-UTR fragments, the sequence from 1620 to 2792 (~1173 bp) in the human CYP3A4 mRNA (NM_017460.5), containing a putative miR-27b/miR-206/miR-21/miR-130a binding sites or mutated binding sites (reverse binding sites), and human CYP3A5 3′-UTR fragments, the sequence from 552 to 1105(~554 bp) in the human CYP3A5 mRNA (NM_001190484.2), containing a putative miR-27b/miR-142binding sites or mutated binding sites (reverse binding sites), were cloned into the pmiR-RB-REPORT [TM] Vector (Ribobio Co. [score:1]
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[+] score: 39
MiR-151a-3p, miR-181b-5p, miR-320a, miR-328, miR-433, miR-489, miR-572, and miR-663a were downregulated, while miR-101-3p, miR-106b-5p, miR-130a-3p, miR-195-5p, and miR-19b-3p were upregulated. [score:7]
MiR-151a-3p, miR-181b-5p, miR-320a, miR-328, miR-433, miR-489, miR-572 and miR-663a were downregulated, while miR-101-3p, miR-106b-5p, miR-19b-3p, miR-195-5p, miR-130a-3p and miR-27a-3p were upregulated. [score:7]
miR-151a-3p, miR-181b-5p, miR-320a, miR-328, miR-433, miR-489, miR-572 and miR-663a were downregulated while miR-101-3p, miR-106b-5p, miR-19b-3p, miR-195-5p, miR-130a-3p and miR-27a-3p were upregulated. [score:7]
miR-151a-3p (ΔΔCt = -2.01, P = 8.29E-06), MiR-181b-5p (ΔΔCt = -3.39, P = 1.04E-10), miR-320a (ΔΔCt = -2.47, P = 5.02E-12), miR-328 (ΔΔCt = -2.28, P = 4.33E-06), miR-433 (ΔΔCt = -2.33, P = 0.0001), miR-489 (ΔΔCt = -2.10, P = 1.25E-06), miR-572 (ΔΔCt = -2.47, P = 2.66E-08) and miR-663a (ΔΔCt = -2.06, P = 0.00002) were downregulated, while miR-101-3p (ΔΔCt = 1.43, P = 0.003), miR-106b-5p (ΔΔCt = 1.30, P = 0.008), miR-130a-3p (ΔΔCt = 2.35, P = 1.89E-09), miR-195-5p (ΔΔCt = 1.43, P = 0.0016) and miR-19b-3p (ΔΔCt = 1.87, P = 6.88E-09) were upregulated in the ASD individuals. [score:7]
The differentially expressed miRNAs in this study, which included miR-101, miR-106b, miR-130a, miR-151a, miR181b, miR-328, miR-433, miR-489 and miR-572, were previously reported to have altered expression in schizophrenia [31- 35], supporting the contention that ASD and schizophrenia share common neurobiological features [36]. [score:5]
Collectively, these results predicted several neurologically relevant canonical pathways for the target genes of the five miRNAs (miR-130a-3p, miR-19b-3p, miR-320a, miR181b-5p, and miR-572) that showed a good discriminative power in ROC analysis. [score:3]
High values for sensitivity, specificity and the area under the curve (AUC) were observed for five miRNAs: miR-181b-5p, miR-320a, miR-572, miR-130a-3p and miR-19b-3p (see Additional file 6). [score:1]
The Ct values of nine miRNAs (miR-101-3p, miR-106b-5p, miR-151a-3p, miR-195-5p, miR-19b-3p, miR-27a-3p, miR-320a, miR-328, and miR-489) were in the range of 25–30, while the remaining five miRNAs (miR-130a-3p, miR-181b-5p, miR-433, miR-572, and miR-663a) had Ct values in the range of 30 to 35. [score:1]
High values for sensitivity, specificity and area under the curve (AUC) were observed for five miRNAs: miR-181b-5p, miR-320a, miR-572, miR-130a-3p and miR-19b-3p (see Additional file 6). [score:1]
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[+] score: 34
Based on the fold changes, qRT-PCR was performed to validate microarray results on 12 miRNAs, specifically miRNAs up-regulated in both heart and plasma (miR-660-3p, miR-665, miR-1285-3p and miR-4491), down-regulated in heart but up-regulated in plasma (miR-206 and miR-1268b), up-regulated in heart but down-regulated in plasma (miR-130-3p, miR-199a and miR-330-3p), down-regulated in both heart and plasma (miR-221-30, miR-487b-3p and miR-4288), were chosen for validation test in the plasma of 45 control and 45 CHF patients. [score:19]
Interestingly, all upregulated cardiac-enriched miRNAs (upregulated in circulation) were more abundant in fibroblasts compared to cardiomyocytes, which indicated cardiac fibroblast derivation, while miR-130a-3p, which is also cardiac-enriched but down-regulated in circulation, was more abundant in cardiomyocytes (Supplemental Figure 2B). [score:9]
Analysis of miRNAs expression revealed that miR-660-3p, miR-665, miR-1285-3p, miR-4491 and miR-130a-3p were relatively cardiac-enriched, while the remaining miRNAs showed a non-cardiac highly expression patterns (Supplemental Figure 1). [score:5]
As a result, 8 of the 12 selected miRNAs (miR-660-3p, miR-665, miR-1285-3p, miR-4491, miR-206, miR-1268b, miR-130-3p and miR-330-3p) were successfully validated in the second cohort. [score:1]
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[+] score: 33
Increased miR-142-5p expression resulted in decreased SOCS1 expression, while a decrease in miR-130a-5p expression resulted in increased PPARγ expression. [score:9]
Likewise, Lin et al. demonstrated the miR-130a targets PPARγ, a key regulator of immune suppression mechanism, and exhibit antagonistic expression with another M2 Mφ marker, CD163 (114). [score:8]
Mirroring their in vitro results, analysis of MΦ miR-142-5p and miR-130a-5p expression in tissue samples from patients with liver cirrhosis or idiopathic pulmonary fibrosis revealed the same pattern of miRNA-target expression. [score:7]
Their enforced expression inhibits NF-κB activation and cytokine production in mature MΦs(11– 13)Su et al. investigated the miRNA profiles of alternatively activated MΦs and identified miR-142-5p and miR-130a-3p as important contributors to the pro-fibrogenic MΦ program (78). [score:3]
Their enforced expression inhibits NF-κB activation and cytokine production in mature MΦs(11– 13) Su et al. investigated the miRNA profiles of alternatively activated MΦs and identified miR-142-5p and miR-130a-3p as important contributors to the pro-fibrogenic MΦ program (78). [score:3]
By using mouse mo dels of fibrosis, they were also able to demonstrate therapeutic efficacy via the introduction of miR-142-5p inhibitor and miR-130a-3p mimic. [score:3]
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[+] score: 32
A. Expression of miR-21 and miR-23a, B. Expression of miR-30b and miR-130a, C. Expression of miR-133b and miR-191, D. Expression of miR-204 and miR-208b. [score:9]
These miRNAs are miR-30b which has target for Notch1 and Bcl [2] and, miR-130a has target for BMPR1b and SMAD2. [score:5]
The expression of miR-130a and miR-204 did not show any significant pattern changes among the male and female subjects, compared to their total expression. [score:4]
The expression of miR-130a, miR-133b and miR-191 were increased significantly in all PH subjects and, showed further pronounced in severe PH subjects. [score:3]
The expression of miR-130a showed a 2.54±0.56-fold (p<0.05) enhancement in moderate PH where severe PH showed a sharp increment of 9.27±1.19-fold (p<0.01), respectively. [score:3]
During moderate PH, miR-21, miR-23b, miR-130a, miR-491 and miR-1246 are moderately upregulated but, are more pronounced in severe PH, compared to the controls. [score:3]
However, the expression of miR-130a and miR-208b were significant in severe PH subjects, compared to their moderate counterparts. [score:2]
Interestingly, miR-23b and miR-130a showed target genes for BMPR1b which is degraded during PH and considered as a predictor for PH [33], [34]. [score:2]
From this study, we present evidence that a set of increased plasma miRNA level that include miR-21, miR-130a, miR-133b, miR-191, miR-204 and miR-208b, can be used as biomarker for assessment of PH. [score:1]
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[+] score: 30
CDK4, APPBP2, ZNF10, CDK13, and AKTIP are inhibited by let-7d, APPBP2 is inhibited by mir-200a, KLC1, FLNB, MYBL1, and GCN1L1 are inhibited by mir-223, FBXW7, ZNF274, and IRF8 are inhibited by mir-130a, and FUBP1 is inhibited by mir-25. [score:11]
In addition, FLNB is inhibited by mir-223 (c [il] = −0.21954), CDK4 is inhibited by miRNA let-7d (c [il] = −0.50305), and ZNF274 is inhibited by mir-130a (c [il] = −0.10597). [score:7]
Therefore, drugs designed to target these DNA methylated genes (BTG3, G0S2 and AP2B1) or genes inhibited by miRNAs, mir-223, let-7d, and mir-130a (FLNB, CDK4 and ZNF274) may delay aging. [score:5]
We found that in the specific core GEN of elderly individuals, FLNB, CDK4, and ZNF274 are inhibited by mir-223, let-7d, and mir-130a, respectively, and DNA methylation of FYN, CDK4, MAGED1 and ZNF274 in order to overcome dysregulation of the MAPK signaling, T-cell receptor signaling, and neurotrophin signaling pathways, as well as deregulated cell cycle and apoptosis processes. [score:5]
We observed that there are three core miRNAs, mir-223, let-7d and mir-130a, that regulate FLNB, CDK4, and ZNF274, respectively (Figure 10). [score:2]
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[+] score: 30
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-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-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-16-2, hsa-mir-197, hsa-mir-199a-1, hsa-mir-208a, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-199a-2, hsa-mir-204, hsa-mir-210, hsa-mir-181a-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-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-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-138-2, hsa-mir-140, 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-138-1, hsa-mir-146a, hsa-mir-193a, hsa-mir-194-1, 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-194-2, hsa-mir-106b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-34b, hsa-mir-34c, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-363, hsa-mir-365a, hsa-mir-365b, hsa-mir-369, hsa-mir-370, hsa-mir-371a, hsa-mir-375, hsa-mir-378a, hsa-mir-133b, hsa-mir-423, hsa-mir-448, hsa-mir-429, hsa-mir-486-1, hsa-mir-146b, hsa-mir-181d, hsa-mir-520c, hsa-mir-499a, hsa-mir-509-1, hsa-mir-532, hsa-mir-33b, hsa-mir-637, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-509-2, hsa-mir-208b, hsa-mir-509-3, 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-371b, hsa-mir-499b, hsa-mir-378j, hsa-mir-486-2
[192] miR-33b Decrease lipogenesis via early B cell factor 1 (EBF1) targeting C/EBPα and PPARγ signaling[193] miR-93 Sirt7 and Tbx3[194] miR-125a ERRα[195] miR-130 Inhibition of adipogenesis by inhibiting PPARγ[66] miR-138 Inhibition of adipocyte differentiation via EID-1. Lipid droplet reduction[196] miR-145 Preadipocyte differentiation by targeting IRS1[197] miR-155 C/EBPβ pathway[198] mirR-193a/b Adiponectin production in the adipose tissue. [score:11]
The overexpression of miR-27a and miR-130a clearly suppresses adipocyte differentiation along with PPARγ expression. [score:7]
Another notable example is given by miR-27a and miR-130a that inhibit adipocyte differentiation through PPARγ downregulation [65, 66]. [score:6]
Lower expression levels of miR-130a and miR-130b have been reported in the abdominal subcutaneous adipose tissue and in the plasma of obese women compared with those of lean subjects [67]. [score:2]
Activation of serotonin receptors 5-HT2AR and 5-HT2CR[203] miR-709 GSK3ß of Wnt/ß-catenin signaling[204] miR-143 and miR-130 are the best studied among the miRNAs linked to adipogenesis. [score:1]
Alterations in circulating miR-23a, miR-27a, miR-130, miR-195, miR-197, miR-320a, and miR-509-5p have been associated to metabolic syndrome [153, 154]. [score:1]
Additionally, circulating miR-130a and miR-195 have been connected with high blood pressure [153]. [score:1]
Activation of serotonin receptors 5-HT2AR and 5-HT2CR[203] miR-709 GSK3ß of Wnt/ß-catenin signaling[204] miR-143 and miR-130 are the best studied among the miRNAs linked to adipogenesis. [score:1]
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[+] score: 26
miR-130a expression in the HCV-infected liver is much higher than in control, and miR-130a knockdown also inhibits HCV RNA replication in hepatocytes by inducing IFITM1 expression [29], which, in turn, stimulates secretion of IFN. [score:8]
Further, miR-130a was found to downregulate miR-122 but upregulate proteins that coordinate the host innate immune response, including type I IFN (IFNα/IFNβ), ISG15, USP18, and MxA. [score:7]
On the other hand, miR-130a overexpression was also reported to suppress HCV RNA replication in both the Con1b replicon and in the JFH1 -based cell culture system [30]. [score:5]
Thus, HCV may persist by up -regulating miR-130a to inhibit IFITM1 and the subsequent innate immune response. [score:4]
The role of miR-130a in HCV infection is similarly complex. [score:1]
Collectively, the data indicate that miR-130a may play dual roles in HCV replication by shaping the host innate immune response. [score:1]
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[+] score: 26
As shown in Figure 2F, overexpression of miR-1305 abolished the up-regulated expression of Sox9, miR-130a, as well as miR-145, which indicated the inhibition of DANCR-facilitated chondrogenesis. [score:10]
In addition, the expression of chondrogenic specific markers Sox9, miR-130a, and miR-145 were also detected with the down-regulation of Smad4. [score:6]
As shown in Figure 4E, depletion of Smad4 decreased the expression level of Sox9, miR-130a, and miR-145 that was induced by DANCR. [score:3]
The result showed that SMSCs with highly expressed DANCR exhibited significantly increased abundance of Sox9, miR-130a, and miR-145 (Figure 1F). [score:3]
The chondrogenic differentiation was determined by detecting the expression of chondrogenic-specific markers including Sox9, miR-130a, and miR-145. [score:3]
The relative expression level of miR-130a, miR-145, and miR-1305 were calculated with the 2–ΔΔ C [t] method. [score:1]
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[+] score: 24
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-23a, hsa-mir-25, hsa-mir-26a-1, 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-100, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-16-2, hsa-mir-198, hsa-mir-199a-1, hsa-mir-148a, 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-199a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-204, hsa-mir-210, hsa-mir-212, hsa-mir-181a-1, hsa-mir-214, hsa-mir-215, hsa-mir-216a, hsa-mir-217, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-let-7g, hsa-let-7i, hsa-mir-15b, 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-135a-1, hsa-mir-135a-2, hsa-mir-142, 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-134, hsa-mir-146a, hsa-mir-150, hsa-mir-186, hsa-mir-188, hsa-mir-193a, hsa-mir-194-1, hsa-mir-320a, hsa-mir-155, hsa-mir-181b-2, hsa-mir-128-2, hsa-mir-194-2, hsa-mir-106b, hsa-mir-29c, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-99b, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-362, hsa-mir-369, hsa-mir-375, hsa-mir-378a, hsa-mir-382, hsa-mir-340, hsa-mir-328, hsa-mir-342, hsa-mir-151a, hsa-mir-148b, hsa-mir-331, hsa-mir-339, hsa-mir-335, hsa-mir-345, hsa-mir-196b, hsa-mir-424, hsa-mir-425, hsa-mir-20b, hsa-mir-451a, hsa-mir-409, hsa-mir-484, hsa-mir-486-1, hsa-mir-487a, hsa-mir-511, hsa-mir-146b, hsa-mir-496, hsa-mir-181d, hsa-mir-523, hsa-mir-518d, hsa-mir-499a, hsa-mir-501, hsa-mir-532, hsa-mir-487b, hsa-mir-551a, hsa-mir-92b, hsa-mir-572, hsa-mir-580, hsa-mir-550a-1, hsa-mir-550a-2, hsa-mir-590, hsa-mir-599, hsa-mir-612, hsa-mir-624, hsa-mir-625, hsa-mir-627, hsa-mir-629, hsa-mir-33b, hsa-mir-633, hsa-mir-638, hsa-mir-644a, hsa-mir-650, hsa-mir-548d-1, hsa-mir-449b, hsa-mir-550a-3, hsa-mir-151b, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-454, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-708, hsa-mir-216b, hsa-mir-1290, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-378b, hsa-mir-3151, hsa-mir-320e, hsa-mir-378c, hsa-mir-550b-1, hsa-mir-550b-2, 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, hsa-mir-486-2
Finally, expression of miR-130a and miR-130b, controlled by BCR-ABL, down-regulated the expression of CCN3, a growth inhibitory protein [39]. [score:10]
Consistent with the notion that miR-130a can act as a tumor suppressor by targeting BCL2 and MCL-1 expression, lower expression of miR-130a is associated with poor prognosis as indicated by shorter overall survival and treatment-free survival in CML patients [55]. [score:9]
It should be noted that the tyrosine kinase inhibitor (TKI) Dasatinib affected miR-let-7d, miR-let-7e, miR-15a, miR-16, miR-21, miR-130a and miR-142-3p expressions, while Imitanib affected miR-15a and miR-130a levels [47]. [score:5]
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Lee E. K. Lee M. J. Ab delmohsen K. Kim W. Kim M. M. Srikantan S. Martindale J. L. Hutchison E. R. Kim H. H. Marasa B. S. miR-130 Suppresses Adipogenesis by Inhibiting Peroxisome Proliferator-Activated Receptor γ Expression Mol. [score:7]
These include the miR-130 family members that repress brown and white adipogenesis via direct inhibition of Pparg [30] and miR-378 that activates Cebpa and Cebpb expression during adipogenesis and enhances brown fat expansion [31, 32]. [score:6]
Expression of miR-130 is increased in adipocyte hypertrophy and fat inflammation [41] and interestingly, miR-130 of the current Fto- KO BAT was significantly decreased in comparison with WT, indicating a role for FTO in the regulation of miR-130 and the pathophysiology of obesity. [score:4]
PPARγ and C/EBPβ are important transcription factors in both brown and white adipogenesis and are inhibited by miR-130 and miR-155, respectively [30, 33]. [score:3]
Kim C. Lee H. Cho Y. M. Kwon O. J. Kim W. Lee E. K. TNFα-Induced miR-130 Resulted in Adipocyte Dysfunction during Obesity-Related Inflammation FEBS Lett. [score:1]
In addition, miR-130 was reported to be increased in WAT of mice due to HFD [41], which was also observed in our WT mice but not in the Fto- KO mice. [score:1]
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[+] score: 21
Several examples are: miR-17-92 which is upregulated in colonocytes coexpressing K-Ras and c-Myc, represses the expression of anti-angiogenic thrombospondin-1 (Tsp1) and connective tissue growth factor (CTGF), thus induces angiogenesis [17]; miR-378 promotes angiogenesis induced by human glioblastoma cell line U87 by targeting Fus-1 expression [18]; miR-126 regulates vascular integrity and angiogenesis, and miR-126 restoration decreases VEGF level in lung cancer cells [19], [20]; miR-130a mediates angiogenesis through downregulating antiangiogenic homeobox genes GAX and HOXA5 [21]; miR-296 level is elevated in primary brain tumor endothelial cells and regulates angiogenesis by directly targeting the hepatocyte growth factor-regulated tyrosine kinase substrate mRNA, leading to the reduction of HGS -mediated degradation of the growth factor receptors VEGFR2 and PDGFRbeta [22]. [score:21]
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[+] score: 21
The EMT-related genes, miR-200b, miR-130a, zeb2, and E-cadherin were also upregulated by demethylating agents. [score:4]
To explore the mechanisms underlying the upregulation of miRNAs in endometrial cancers, we examined the methylation status of miR-130a, miR-130b, miR-625 and miR-200b by bisulfite-specific PCR sequencing (Table  1). [score:4]
Aberrant expression of miRNAs including miR-200b, miR-130a/b, miR-625 and miR-222 was associated with tumorigenesis and metastasis in endometrial cancer. [score:3]
In this study we showed that specific miRNAs, particularly miR-130a/b and miR-200 family, were crucially involved in gene expression during EMT and the subsequent accumulation of malignant features. [score:3]
In this present study we found that aberrant expression of miRNAs including miR-200b, miR130a/b, miR-625 and miR-222 was associated with tumorigenesis and metastasis in endometrial cancer. [score:3]
Here we presented for the first time a comprehensive analysis of miR-130 family and DICER1 expression in endometrial cancer tissues, compared with normal endometrium. [score:2]
miR-130a/b, miR-200b, and miR-625 contain several CpG sites in their upstream regulatory sequences. [score:2]
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[+] score: 19
Seven miRNAs (downregulated: miR-29c, miR-93, miR-101 and miR-130a; upregulated: miR-9, miR-182 and miR-221) were identified as differentially expressed (≥2-fold) in both A172-TR and U251-TR cell lines (Figure 1A). [score:9]
Upregulated miRNAs (miR-9, miR-182 and miR-221) were shown in red, downregulated miRNAs (miR-29c, miR-93, miR-101 and miR-130a) were shown in green. [score:7]
The expression of two other miRNAs (miR-130a and miR-221) didn't change significantly (p>0.05). [score:3]
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[+] score: 19
Strong inverse correlation was observed between the tumor suppressor PTEN and several members of the miR-17, miR-19, miR-130/301 and miR-26 families, which were upregulated in the osteosarcoma cell lines. [score:6]
In addition, the expression of the tumor suppressor gene phosphatase and tensin homolog (PTEN) inversely correlated with miR-17, miR-20b, miR-9* and miR-92a (Table 2), but also showed a modest inverse correlation (r = −0.4 to −0.5) with other miRNAs of the miR-17, miR-19, miR-130/301 and miR-26 families (Table S6). [score:5]
Furthermore, the upregulated miRNAs included miR-9/miR-9*, miR-21*, miR-31/miR-31*, miR-196a/miR-196b, miR-374a and members of the miR-29 and miR-130/301 families. [score:4]
Furthermore, the overexpressed miRNAs included miR-7, miR-9/miR-9*, miR-21*, miR-31/miR-31*, miR-181, miR-196a/miR-196b, miR-503 and members of the miR-29 and miR-130/301 families (Table 1). [score:3]
PTEN mRNA correlated inversely with miR-92a and members of the miR-17 and miR-130/301 families. [score:1]
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28
[+] score: 18
miRNA-31 downregulation conferred resistance to radiotherapy and chemotherapy in several types of cancers [37], [38], and downregulation of miRNA-30a [39], miRNA-203 [40], miRNA-183 [41], miRNA-130a [42], miRNA-24 [43] and miRNA-23a [43], and upregulation of miRNA-193b [44] increased tumor cells resistant to chemotherapy. [score:10]
Our results showed that miRNA-23a, miRNA-203, miRNA-31, miRNA-30a, miRNA-183, miRNA-130a, and miRNA-24 were downregulated, and miRNA-193b upregulated in the radioresistant NPC cells, suggesting that deregulation of these miRNAs might be involved in the NPC radioresistance. [score:8]
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29
[+] score: 17
From the real-time RT-PCR analysis, down-regulation of TP53INP1 and up-regulation of miR-130 and miR-155 in MCF7-ADR as compared with MCF-7 (Figure 2F and 2G). [score:6]
These included miR-130 and miR-155 also known as TP53INP1 binding miRNAs, and most of them are highly expressed in MCF7-ADR, indicating that these miRNAs and TP53INP1 expressions were inversely correlated. [score:5]
Taqman probes for human were used to assess the expression levels of miRNAs (hsa-miR-505, ID: 4373230, hsa-miR-130, ID: 000454, and hsa-miR-155, ID: 002623). [score:3]
One of them is tumor protein p53 inducible nuclear protein 1 (TP53INP1) (Figure 2D), which has been recently shown to be suppressed by several miRNAs such as miR-130 and miR-155 [16, 17]. [score:3]
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30
[+] score: 15
Decreased expression of microRNA-130a correlates with TNF-α in the development of osteoarthritis. [score:4]
miR-130a play an important role in regulating the expression of TNF-α in human chondrocytes (Li et al., 2015). [score:4]
Besides miR-130a, miR-1234(AUC 0.9048, 95% CI 0.7881–1.021, p = 0.00047) and miR-451a (AUC 0.9221, 95% CI 0.7852–1.059, p = 0.00038) had an AUC > 0.90. [score:1]
In addition, significant correlations were found for miR-1290 (r = −0.2706, p < 0.05), miR-130a (r = −0.2984, p < 0.05), and miR-1234 (r = −0.3545, p < 0.05) with total serum BALP of individuals at total time points respectively. [score:1]
Meantime, miR-130a (r = −0.5439, p < 0.05) and miR-1234 (r = −0.7367, p < 0.01) were significantly associated with serum BALP at 45 day of bed rest (Table 5). [score:1]
Table 7 showed serum PICP at total time points were significantly associated with miR-363 (r = −0.3347 p < 0.05), miR-1290 (r = −0.2908, p < 0.05), miR-103 (r = −0.2739, p < 0.05), miR-451a (r = −0.3204, p < 0.05), miR-130a (r = −0.3402, p < 0.05), miR-1234 (r = −0.2396, p < 0.05), and miR-20a (r = −0.3148, p < 0.05), respectively. [score:1]
As shown in Figure 4, the AUC of miR-130a was the highest, reaching 0.9881 (95% confidence interval [CI] 0.9674–1.019, p < 0.0001). [score:1]
The sensitivity and specificity associated with the optimal cut-off points are shown in Table 2. miR-130a showed the highest sensitivity of 92.6% and a specificity of 100%. [score:1]
At 45 days of bed rest, miR-451a (r = −0.5007, p < 0.05) and miR-1234 (r = 0.7418, p < 0.01) had significant positive correlations with serum PICP, and only miR-130a (r = −0.5859, p < 0.05) were significantly associated with serum PICP at 10 days of recovery. [score:1]
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31
[+] score: 15
In addition, miR-451, miR-27a, miR-21, miR-130a, miR-let-7, miR-137, miR-200c, miR-122, miR-138 and miR-10a/b were suggested to regulate ABCB1 gene expression indirectly by targeting other mRNAs that code the proteins associated with the activation of ABCB1 gene expression [72, 73, 74, 75, 76, 77, 78, 79]. [score:9]
Yang L. Li N. Wang H. Jia X. Wang X. Luo J. Altered microRNA expression in cisplatin-resistant ovarian cancer cells and upregulation of miR-130a associated with MDR1/P-glycoprotein -mediated drug resistance Oncol. [score:6]
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32
[+] score: 15
Recent studies indicate that connexin 43, a major cardiac gap junction protein, is a direct target of miRNA-130a and that over -expression of miRNA-130a may contribute importantly to gap junction remo deling and to the pathogenesis of atrial and ventricular arrhythmias [82]. [score:6]
Chen and Gorski [97] showed that miRNA-130a regulates angiogenic phenotype of vascular ECs through down-regulation of anti-angiogenic homeobox genes GAX and HOXA5 [97]. [score:5]
Osbourne A. Calway T. Broman M. McSharry S. Earley J. Kim G. H. Downregulation of connexin43 by microRNA-130a in cardiomyocytes results in cardiac arrhythmias J. Mol. [score:4]
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33
[+] score: 14
In line with this result, an inhibitor of MiR-130a was found to reverse the cisplatin resistance by upregulating the expression of PTEN and downregulating P-glycoprotein (P-gp) in A2780 cell lines (89). [score:10]
In addition, miR-93 and miR-130a may also be associated with cisplatin resistance by direct targeting PTEN in ovarian cancer cells (87, 88). [score:4]
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34
[+] score: 13
We also identified EB upregulated miRNAs that have not been previously reported such as miR-130a, miR-301a, and miR-135, miR-190, miR-30c, and miR-30e. [score:4]
The expression of miR-106a, miR-106b, miR-17-5p, miR-92, miR-93, miR-190, miR-20a and miR-130 were highest in EB (panel B). [score:3]
For miR-106b, miR-92, miR-93, miR-130a and miR-190, the difference in their expression between EB and hES cells and between EB and adult cells were significant (P < 0.05). [score:3]
The expression of miR-106a, miR-106b, miR-17-5p, miR-92, miR-93, miR-130a, miR-20a and miR-190 were much higher in EB than in either hES cells or adult cells (Figure 6, panel B). [score:3]
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35
[+] score: 13
Other miRNAs from this paper: hsa-mir-33a, hsa-mir-155, hsa-mir-130b, hsa-mir-33b
Accordingly, by using a CMV promoter -driven reporter harboring the 3′ UTR of MafB mRNA, we found that MafB expression could be inhibited by co-expressed miR-155 (Fig.   6b), to an extent similar to inhibition mediated by miR-130, a previously reported MafB -targeting microRNA [31]. [score:11]
Effect of miR-130 ectopic expression was compared as a positive control. [score:2]
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36
[+] score: 12
Specifically, motif A, which involves the TF CEBPB, the miRNA hsa-mir-130 and various target genes, is an example of how co-regulatory network motifs may help to better understand the pathogenicity of PD. [score:4]
However, Lee and colleagues 2008 demonstrated that hsa-mir-130 regulates ATXN protein levels in human cells and its inhibition enhances the cytotoxicity caused by the ATXN protein 55, 56. [score:4]
This sheds light on the potential collaborative role between the hub gene CEBPB and the hub miRNA hsa-mir-130 and their co-regulated genes/miRNAs in regulating ATXN. [score:3]
Additionally, the miRNAs mir-130, mir-636, and mir-744 are involved in subnetworks created from enriched GO terms corresponding to abnormal adult neurogenesis, apoptosis, and cell death. [score:1]
[1 to 20 of 4 sentences]
37
[+] score: 12
Among the 87 most-variable expressed miRNAs across the entire panel, a group of 15 miRNAs (hsa-miR-130a, hsa-miR-886-5p, hsa-miR-886-3p, hsa-miR-222, hsa-miR-21*, hsa-miR-29a, hsa-miR-23a, hsa-miR-24, hsa-miR-30a, hsa-miR-27a, hsa-miR-22, hsa-miR-532-3p, hsa-miR-100, hsa-miR-125b, hsa-miR-221) was significantly higher expressed in the minor cluster as opposed to other miRNAs (Figure 2, top red box). [score:5]
The top four most significantly associated miRNAs - hsa-miR-130a (11q12.1), hsa-miR-22 (17p13.1), hsa-miR-93 (7q22.1) and hsa-miR-383 (8p22) - with DNA CNVs in breast cancer cell lines are shown in Figure 6. Figure 6 Association of miRNA expression with genomic copy number variation in breast cancer cell lines. [score:3]
The top four most significantly associated miRNAs - hsa-miR-130a (11q12.1), hsa-miR-22 (17p13.1), hsa-miR-93 (7q22.1) and hsa-miR-383 (8p22) - with DNA CNVs in breast cancer cell lines are shown in Figure 6. Figure 6 Association of miRNA expression with genomic copy number variation in breast cancer cell lines. [score:3]
The majority of these miRNAs (hsa-miR-130a, hsa-miR-93, hsa-miR-383, hsa-miR29c, hsa-miR-382, hsa-miR-31) were already found to be located in regions that exhibited DNA copy number abnormalities in breast cancer tumors [65]. [score:1]
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38
[+] score: 12
There are also a number of miRNAs such as miR-132, miR-212, miR-130a and miR-152 shown to be upregulated in the pancreatic islets of the wi dely-studied T2D mo del Goto-Kakizaki rats (Esguerra et al., 2011) with active roles in beta cell stimulus-secretion coupling (Malm et al., 2016; Ofori et al., 2017). [score:4]
Expression of miR-200a, miR-130a and miR-152 in INS-1 832/13 cells (A–C) or in EndoC-βH1 cells (D–F) at different confluences. [score:3]
For miR-200a, miR-130a and miR-152, the expression levels were found not to be influenced by cellular confluence (Fig. S2). [score:3]
We also investigated the influence of confluence on the expression levels of miR-200a, miR-130a, miR-152, miR-132 and miR-212. [score:1]
The following primers from TaqMan [®] Gene Expression and TaqMan [®] miRNA Assays were used for qPCR: Cav1/CAV1 (Rn00755834_m1/Hs00971716_m1), Aifm1/AIFM1 (Rn00442540_m1/ Hs00377585_m1), miR-375 (TM_ 000564), miR-200a (TM_000502), miR-130a (TM_00454), miR-152 (TM_000475), miR-132 (TM_000457) and miR-212 (TM_002551) were used for qPCR. [score:1]
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39
[+] score: 12
The top downregulated lung TIC -associated miRNAs include miR-23a, miR-130a, let-7 family, miR-513a-5p, miR-125b and miR-29a, whereas the top upregulated miRNAs include miR-1290, miR-130b, miR-1246, miR-630, miR-196a/b, miR-9/9* and miR-17∼92 cluster and its miR-106b∼25 analogues. [score:7]
Similarly, miR-23a and miR-130a were shown to be downregulated in chronic myeloid leukaemia 29, and miR-29a/b/c was frequently reduced in a variety of cancers that include lung cancer 30. [score:4]
Taqman miRNA probes were as follow: hsa-miR-1246 (462575_mat), hsa-miR-1290 (002863), hsa-miR-130a (000454), hsa-miR-130b (000456), hsa-miR-196a (241070_mat), hsa-miR-196b (002215), hsa-miR-630 (001563), hsa-let-7b-5p (002619), hsa-let-7c (000379), hsa-let-7d-5p (002283), hsa-let-7i (002221), hsa-miR-106b (000442), hsa-miR-125b (000449), hsa-miR-23a (000399), hsa-miR-25 (000403), hsa-miR-320c (241053_mat), hsa-miR-3667-5p (462350_mat), hsa-513-5p (002090), hsa-miR-9* (002231). [score:1]
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40
[+] score: 12
Other groups similarly found that miR-130a is regulated by YAP [89, 282], and YAP -induced tumorigenesis can be reversed by inhibition of miR-130a [89]. [score:4]
Bertero T. Cottrill K. A. Annis S. Bhat B. Gochuico B. R. Osorio J. C. Rosas I. Haley K. J. Corey K. E. Chung R. T. A YAP/TAZ-miR-130/301 molecular circuit exerts systems-level control of fibrosis in a network of human diseases and physiologic conditionsSci. [score:3]
Bertero and colleagues found that YAP/TAZ activation promoted the expression of the miR-130/301 family, which in turn enhanced collagen deposition and ECM remo deling to further enhance YAP activity [365]. [score:3]
Shen S. Guo X. Yan H. Lu Y. Ji X. Li L. Liang T. Zhou D. Feng X. H. Zhao J. C. A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesisCell Res. [score:1]
Bertero T. Cottrill K. A. Lu Y. Haeger C. M. Dieffenbach P. Annis S. Hale A. Bhat B. Kaimal V. Zhang Y. Y. Matrix remo deling promotes pulmonary hypertension through feedback mechanoactivation of the YAP/TAZ-miR-130/301 circuitCell Rep. [score:1]
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41
[+] score: 12
The boxplots show significant downregulation of miR-130a-3p a, miR-149-5p b, miR-423-5p c, miR-487b-3p d and miR-193b-3p e in the FET placentae. [score:4]
Of these miRNAs, four (miR-130a-3p, miR-149-5p, miR-423-5p, and miR-487b-3p) were significantly downregulated in FET placentae compared with those from SP and ET. [score:3]
We identified four miRNAs, miR-130a-3p, miR-149-5p, miR-423-5p, and miR-487b-3p, that were significantly downregulated in FET placentae compared with those from SP and ET. [score:3]
We found that expression of miR-130a-3p, miR-149-5p, miR-423-5p, and miR-487b-3p was decreased in the term placentae derived from FET compared with those derived from ET or SP. [score:2]
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42
[+] score: 11
5) 7 hsa-mir-19a dbDEMC 32 hsa-mir-30d dbDEMC 8 hsa-mir-92a HMDD, miR2Disease 33 hsa-mir-451 literature 9 hsa-mir-210 miR2Disease 34 hsa-mir-152 dbDEMC 10 hsa-mir-19b dbDEMC, miR2Disease 35 hsa-mir-215 dbDEMC 11 hsa-mir-224 dbDEMC, miR2Disease 36 hsa-mir-130a dbDEMC, HMDD 12 hsa-let-7f dbDEMC, miR2Disease 37 hsa-mir-499 higher RWRMDA (No. [score:11]
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43
[+] score: 11
In this sense, by virtue of miRNAs known mechanism of action, reducing gene expression by binding to the 3'UTR of their targeted genes, a number of evidenced miRNA species (Mir-27a, Mir-103, Mir-17-5p and Mir-130a) might be involved in turning off the 'neuron projection morphogenesis' process in the SHVT group. [score:5]
Other deregulated biological processes included ‘blood vessel development’ (Mir-155, Mir-17-5p and Mir-130a) (FDR = 6x10 [-4]), 'lung development' (Mir-17-5p and Mir-27a) (FDR = 4x10 [-4]), and ‘cell motion’ (Mir-103) (FDR = 8x10 [-4]) (S3 Table). [score:3]
A heatmap built from nominally significant miRNAs between SHVT and NA detected by sRNA-seq are shown in S3 Fig. When comparing the direct sequencing of the samples with the bioinformatic prediction, 28 miRNA species overlapped, from which Mir-27a, Mir-103, Mir-17-5p, Mir-130a, and Mir-155 were nominally significant although the abundance of the latter was observed to be opposite to the one deduced by GSEA (Table 2). [score:2]
Interestingly, this process was the only one involving all four miRNA species with a consistent abundance among microarray -based predictions and sRNA-seq experiments (Mir-27a, Mir-103, Mir-17-5p and Mir-130a) (FDR<1x10 [-4]) (S3 Table). [score:1]
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44
[+] score: 11
Other miRNAs from this paper: hsa-mir-26a-1, hsa-mir-130b, hsa-mir-26a-2
In breast cancer cells, high expression of c-myc and subsequent high expression of miR-130a resulted in low HOXA5 expression 17. [score:7]
Similarly, HOXA5 is also regulated by miR-130 in human breast cancer cells 17. [score:2]
Due to the lack of high levels of either c-myc or miR-130a 1, miR-130a is unlikely to play a role in the regulation of HOXA5 in LPS cells. [score:2]
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45
[+] score: 11
severe (p<0.05) cfa-let-7d, cfa-miR-101, cfa-miR-10a, cfa-miR-1296, cfa-miR-1306, cfa-miR-1307, cfa-miR-130a, cfa-miR-136, cfa-miR-17, cfa-miR-181b, cfa-miR-196b, cfa-miR-197, cfa-miR-215, cfa-miR-22, cfa-miR-30d, cfa-miR-33b, cfa-miR-497, cfa-miR-503, cfa-miR-574, cfa-miR-628, cfa-miR-676 Comparing the miRNA differential expression analyses between disease states obtained by RT-qPCR and RNAseq, we observed discordances between the two methods. [score:5]
severe (p<0.05) cfa-let-7d, cfa-miR-101, cfa-miR-10a, cfa-miR-1296, cfa-miR-1306, cfa-miR-1307, cfa-miR-130a, cfa-miR-136, cfa-miR-17, cfa-miR-181b, cfa-miR-196b, cfa-miR-197, cfa-miR-215, cfa-miR-22, cfa-miR-30d, cfa-miR-33b, cfa-miR-497, cfa-miR-503, cfa-miR-574, cfa-miR-628, cfa-miR-676Comparing the miRNA differential expression analyses between disease states obtained by RT-qPCR and RNAseq, we observed discordances between the two methods. [score:5]
severe (p<0.05) cfa-let-7a, cfa-let-7b, cfa-let-7c, cfa-let-7f, cfa-miR-127, cfa-miR-1271, cfa-miR-130a, cfa-miR-139, cfa-miR-17, cfa-miR-1836, cfa-miR-1837, cfa-miR-20a, cfa-miR-23a, cfa-miR-25, cfa-miR-26a, cfa-miR-29b, cfa-miR-378, cfa-miR-421, cfa-miR-502, cfa-miR-503, cfa-miR-542, cfa- miR-652, cfa-miR-653, cfa-miR-872 Normal and mild vs. [score:1]
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46
[+] score: 10
Other miRNAs from this paper: hsa-mir-23b, hsa-mir-122, hsa-mir-130b
Lee E. K. Lee M. J. Ab delmohsen K. Kim W. Kim M. M. Srikantan S. Martindale J. L. Hutchison E. R. Kim H. H. Marasa B. S. miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression Mol. [score:7]
Our results demonstrate that miR-130 potentiates the invasive behavior of HCC cells and may contribute to tumor metastasis by inhibiting PPAR-γ and promoting EMT. [score:3]
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47
[+] score: 10
Another study in HC [70], However, found that miR-133b showed downregulation and might act as tumour suppressor, then, the participants accepted transarterial chemoembolization (TACE) using chemotherapy agents-doxorubicin and cisplatin, miR-133b and othter 11 miRNAs were significantly upregulated in the patients group of nonresponders compared to responders, so research suggests 12 miRNAs might be cooperatively associated with the development of resistance to doxorubicin-cisplatin combined treatment, the underlying cause was that 3 miRNAs among theser miRNAs are directly linked to drug resistance in cancer, especially miR-27a and miR-130a can stimulate MDR1 -mediated drug resistance in HC cells, it had been identified that multidrug resistance protein 1(MDR1 or ABCB1) involved in doxorubicin and cisplatin resistance [71, 72]. [score:10]
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48
[+] score: 10
In our postmortem brain study, we identified a differentially expressed microRNA miR-130a in the PFC of AUD subjects, and expression levels of miR-130a and several predicted target genes (including JARID2 and ITPR2) were negatively correlated [32], indicating ethanol -induced gene expression changes may also be mediated by microRNA regulatory pathways. [score:10]
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49
[+] score: 10
For instance, miR-23a participates in estrogen deficiency -induced gap junction remo deling of rats by targeting GJA1 [33], while miR-130a was found to downregulate GJA1, resulting in cardiac arrhythmias [34]. [score:6]
Osbourne A. Calway T. Broman M. McSharry S. Earley J. Kim G. H. Downregulation of connexin43 by microRNA-130a in cardiomyocytes results in cardiac arrhythmias J. Mol. [score:4]
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50
[+] score: 10
Other miRNAs from this paper: hsa-mir-129-1, hsa-mir-222, hsa-mir-129-2
Shen et al. found that miR-130a, a direct downstream target of YAP, effectively suppressed the tumor suppressor function of vgll4. [score:8]
Shen S. Guo X. Yan H. Lu Y. Ji X. Li L. Liang T. Zhou D. Feng X. H. Zhao J. C. A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis Cell Res. [score:1]
Thus, the YAP-miR-130a-vgll4 positive feedback loop was proposed to function downstream of Hippo signaling to mediate potent responses, and play an important role in liver tumorigenesis [85]. [score:1]
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51
[+] score: 10
“Phototox-miRs” 130a, 93* and 25 showed clear involvement in PDT insensitivity mechanisms corresponding to hypothesis (ii): overexpression of miR-130a could theoretically lead to more efficient PDT in resistive cell lines affecting ROS detoxification (GSH, Sestrins, [49, 50], PRDX3, [51]), adaptation to ROS stress (destabilizing/decreasing HIF-1α [52, 53, 54, 55], SIRT7 and SIRT6, [47, 56]), down-regulation of pro-angiogenic factors (enriched targets in the GO term “positive regulation of angiogenesis”, [55, 57], NOS3, [58, 59, 60, 61]) and survival signaling, such as Akt/PI3-K and NF-κB activation [62, 63, 64, 65]. [score:9]
Interestingly, phototox-miR-130a was the only miR in our study correlating significantly with GSH levels (negative correlation). [score:1]
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52
[+] score: 10
For instance, the transcriptional factor MAFB (V-maf musculoaponeurotic fibrosarcoma oncogene homolog B) is up-regulated during megakaryocyte differentiation upon a significant reduction of miR-130a [15]; miR-155 is also down-regulated which is accompanied by an increase in the expression of Ets-1 and Meis1 (Meis homeobox 1), two transcriptional factors that are important for megakaryocyte development [18]. [score:10]
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53
[+] 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-135a-1, hsa-mir-135a-2, hsa-mir-140, 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
In addition, integration of copy number and expression data in these samples showed overexpression of miR-100, miR-125b-1, and miR-130a (on chromosome 11, and members of the MG-B cluster) as a consequence of chromosomal gain or amplification [49]. [score:5]
The retinoblastoma binding protein 8 gene (RBBP8) is a predicted target of miR-31, miR-126, miR-130a, and miR-335 and is a putative tumor suppressor. [score:5]
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54
[+] score: 10
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-133a-1, hsa-mir-133a-2, hsa-mir-140, 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
miRNA Embryonic age Expression profile mir15a 48 and 72 hpf Midbrain, MHB, notochord mir15b 48 and 72 hpf Midbrain, neurocranium, notochord mir23b 30, 48, and 72 hpf Somites, lens, pharyngeal arches, notochord mir27b 48 and 72 hpf mir30c 48 and 72 hpf Brain, neurocranium, eye, heart mir130a 48 and 72 hpf Brain, gut tube, heart, eye mir133b 30, 48, and 72 hpf Notochord mir301a 48 and 72 hpf Forming cartilage Midbrain, neurocranium, eye, trigeminal ganglia Figure 5 Expression of mir23b in zebrafish embryos. [score:5]
miRNA Embryonic age Expression profile mir15a 48 and 72 hpf Midbrain, MHB, notochord mir15b 48 and 72 hpf Midbrain, neurocranium, notochord mir23b 30, 48, and 72 hpf Somites, lens, pharyngeal arches, notochord mir27b 48 and 72 hpf mir30c 48 and 72 hpf Brain, neurocranium, eye, heart mir130a 48 and 72 hpf Brain, gut tube, heart, eye mir133b 30, 48, and 72 hpf Notochord mir301a 48 and 72 hpf Forming cartilage Midbrain, neurocranium, eye, trigeminal ganglia Figure 5 Expression of mir23b in zebrafish embryos. [score:5]
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55
[+] score: 9
miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression. [score:7]
These two miRNAs are members of the miR-25 and miR-130 families, respectively, which previously have been identified for regulating cell proliferation (Lee et al., 2011; Xu et al., 2013). [score:2]
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56
[+] score: 9
Among 20 expressed miRNAs, the expression levels of hsa-mir-25, hsa-mir-221, hsa-mir-302b, hsa-mir-363, hsa-mir-372, hsa-mir-199a, hsa-mir-302d, hsa-mir-26a, hsa-mir-320, hsa-mir-744, hsa-mir-152 and hsa-let-7e in the study of Morin et al. exceed those obtained with miRExpress, but the levels of hsa-mir-423, hsa-let-7a, hsa-mir-1, hsa-mir-340, hsa-mir-302a, hsa-mir-130a, hsa-let-7f and hsa-mir-122 in the work by Morin et al. are lower than those obtained from miRExpress (Table 6) (full data are available in additional file 7). [score:9]
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57
[+] 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-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-20a, hsa-mir-21, hsa-mir-28, hsa-mir-29a, hsa-mir-93, hsa-mir-100, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-107, hsa-mir-16-2, hsa-mir-196a-1, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-34a, hsa-mir-181c, hsa-mir-182, hsa-mir-196a-2, hsa-mir-199a-2, hsa-mir-210, hsa-mir-217, hsa-mir-223, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-27b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-137, hsa-mir-138-2, hsa-mir-141, hsa-mir-152, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-134, hsa-mir-138-1, hsa-mir-146a, hsa-mir-150, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-106b, hsa-mir-29c, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-372, hsa-mir-382, hsa-mir-148b, hsa-mir-196b, hsa-mir-424, hsa-mir-448, hsa-mir-449a, hsa-mir-483, hsa-mir-491, hsa-mir-501, hsa-mir-503, hsa-mir-548a-1, hsa-mir-548b, hsa-mir-548a-2, hsa-mir-548a-3, hsa-mir-548c, hsa-mir-548d-1, hsa-mir-548d-2, hsa-mir-320c-1, hsa-mir-548e, hsa-mir-548j, hsa-mir-548k, hsa-mir-548l, hsa-mir-548f-1, hsa-mir-548f-2, hsa-mir-548f-3, hsa-mir-548f-4, hsa-mir-548f-5, hsa-mir-548g, hsa-mir-548n, hsa-mir-548m, hsa-mir-548o, hsa-mir-548h-1, hsa-mir-548h-2, hsa-mir-548h-3, hsa-mir-548h-4, hsa-mir-548p, hsa-mir-548i-1, hsa-mir-548i-2, hsa-mir-548i-3, hsa-mir-548i-4, hsa-mir-320c-2, hsa-mir-548q, hsa-mir-548s, hsa-mir-548t, hsa-mir-548u, hsa-mir-548v, hsa-mir-548w, hsa-mir-548x, hsa-mir-548y, hsa-mir-548z, hsa-mir-548aa-1, hsa-mir-548aa-2, hsa-mir-548o-2, hsa-mir-548h-5, hsa-mir-548ab, hsa-mir-548ac, hsa-mir-548ad, hsa-mir-548ae-1, hsa-mir-548ae-2, hsa-mir-548ag-1, hsa-mir-548ag-2, hsa-mir-548ah, hsa-mir-548ai, hsa-mir-548aj-1, hsa-mir-548aj-2, hsa-mir-548x-2, hsa-mir-548ak, hsa-mir-548al, hsa-mir-548am, hsa-mir-548an, hsa-mir-548ao, hsa-mir-548ap, hsa-mir-548aq, hsa-mir-548ar, hsa-mir-548as, hsa-mir-548at, hsa-mir-548au, hsa-mir-548av, hsa-mir-548aw, hsa-mir-548ax, hsa-mir-548ay, hsa-mir-548az, hsa-mir-548ba, hsa-mir-548bb, hsa-mir-548bc
Interestingly, HCV infection up-regulates miR-21 and miR-130a expression, both of which negatively regulate their target genes known to trigger viral replication in cells, by decreasing HCV -mediated IFN type I (IFN-I) production and disrupting the process of viral entry, respectively [61, 62]. [score:9]
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58
[+] score: 9
Smad4 -mediated stimulation of granulocyte differentiation by TGF-β is tempered by miR-130a expression (Hager et al. 2011). [score:3]
Smad4, however, is targeted by miR-130a, miR-182, miR-205 and miR-483 (Hao et al. 2011, Geraldo et al. 2012, Egawa et al. 2016). [score:3]
2011.381) 21874046 Hager M Pedersen CC Larsen MT Andersen MK Hother C Gronbaek K Jarmer H Borregaard N Cowland JB 2011 MicroRNA-130a -mediated down-regulation of Smad4 contributes to reduced sensitivity to TGF-beta1 stimulation in granulocytic precursors. [score:3]
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59
[+] score: 8
Out of the 485 differentially stabilized transcripts, mRNA targets of miR-29, let-7, miR-137, and miR-130 were stabilized with quiescence while miR-17 and miR-200 targets were stabilized with proliferation. [score:5]
Our analysis of miRNA targets enriched for differential decay between P and CI7 fibroblasts highlight a potential role for the miR-17-92 cluster, and miR-200 in promoting transcript decay in quiescent cells, and miR-130 in promoting transcript decay in proliferating cells. [score:3]
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60
[+] score: 8
This finding highlighted how miR-130a, by targeting c-Met, was able to reduce miR-221/222 expression and, accordingly, TRAIL resistance in NSCLC cells. [score:5]
The relationship between c-Met and miR-221/222 was confirmed by Acunzo et al., which found that miR-130a overexpression reduced miR-221/222 levels in a c-Met -dependent manner. [score:3]
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61
[+] score: 8
For example, Lee and colleagues showed that the combination of miR-130a and miR-495 produced a greater decrease in the expression of the tumor suppressor RUNX3, than either miRNA alone [18]. [score:5]
Targeting of RUNX3 by miR-130a and miR-495 cooperatively increases cell proliferation and tumor angiogenesis in gastric cancer cells. [score:3]
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62
[+] score: 8
In the second study, eight miRNAs were analyzed, finding the upregulation of miR-125b and miR-130a to be associated with R-CHOP chemoresistance [24]. [score:4]
The second study analyzed a group of eight miRNAs (miR-21, miR-29, miR-125b, miR-130a, miR-145, miR-155, miR-200c and miR-451) finding the upregulation of miR-125b and miR-130a to be associated with resistance to R-CHOP treatment [24]. [score:4]
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63
[+] score: 8
HHV-6A infection, but not -6B or −7 infections, induced a decrease in miR-155_2 expression and an increase in miR-1238 expression in thyrocytes, as well as an increase in the expression levels of several autoimmunity -associated miRNAs in T lymphocytes, including miR-16_1, miR34a, miR-130a, miR-143_1, miR-202, miR-301b, miR-302c, miR-449b, miR-451_1, and miR-1238_2. [score:7]
In fact, HHV-6A infection (but not HHV-6B or HHV-7 infection) induced a remarkable increase in several autoimmunity-related miRNAs, namely: miR-16, miR-34a, miR-130a, miR-202, miR-301b, miR-302c, and miR-449b. [score:1]
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64
[+] score: 8
The plexins dimerize with Neuropilin (NP1) to signal the Semaphorin ligand attachment; neuropilin is a predicted high-ranking target of let-7g and miR-130, both brain-expressed miRNAs. [score:5]
The positions of target sites for specific miRNAs (triangles above rectangles, with numbers indicating miR miRNAs, e. g. “130” is “mir-130”) are, in general, distributed nonuniformly. [score:3]
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65
[+] score: 7
Dysregulation of the microRNA let-7e and down-regulation of miR-30c, miR-130a, and miR-335 indicate direct involvement of some miRNAs in the development of chemoresistance [15]. [score:7]
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66
[+] score: 7
Other miRNAs from this paper: hsa-mir-21, hsa-mir-494
We observed that centenarians overexpress seven small noncoding RNAs of which four (scaRNA-17, mir-21, mir-130a, and mir-494) are known to be associated with a range of health-beneficial and life span-enhancing actions including telomerase over -expression in Cajal bodies, neuro-protection in ischemia, cardioprotection, and inhibition of mitochondrial damage and apoptosis [6- 9]. [score:7]
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67
[+] score: 7
Dai et al. have correlated a miRNA signature (downregulation of miR-100, miR-130a, and miR-197 and upregulation of miR-181b, miR-181d, miR-101, and miR-195) in HNSCC cells with multiple drug resistance phenotypes in vitro [84]. [score:7]
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68
[+] score: 7
Also miR-130a showed to be downregulated in all resistant cell lines, and suggested to exert its effect by targeting M-CSF, known to enhance invasiveness and metastasis in OC [23]. [score:6]
In our study, let-7e, miR-30c and miR-130a were negatively correlated to Paclitaxel, but only one patient in our study was treated with Paclitaxel. [score:1]
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69
[+] score: 7
For miR-106b-5p and miR-130a-3p, contrary to our findings, previous studies have reported that they were down-regulated in epilepsy patients and animal mo dels 12 13. [score:4]
We got 361, 48, 8, 19, 87 and 26 intersected targets for let-7d-5p, miR-106b-5p, miR130a-3p, miR-146a-5p, miR-15a-5p and miR-194-5p, respectively (Supplementary Table S3). [score:3]
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70
[+] score: 7
We found that ten of the down-regulated miRNAs (miR101, miR26a, miR26b, miR30a, miR30b, miR30d, miR30e, miR34b, miR-let7 g and miRN140) were grouped together in a functional network (Figure 3A) and nine of the down-regulated miRNAs (miR-130a, miR-133a, miR-142, miR-150, miR15a, miR-16, miR-29b, miR-30c and miR-99a) were grouped together in a second network (Figure 3B). [score:7]
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71
[+] score: 7
For example, miR-106b, miR-107, miR-130a, miR-34 [9], miR-93, miR-155, miR-181a, miR-21, miR-23a, miR-320a [8], miR-193b, miR-320b [13] are significantly up-regulated and miR-148a [11, 14], miR-330-5p [15], miR-373 [16] significantly down-regulated. [score:7]
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72
[+] score: 7
For example, miR-130a and miR-206 inhibit the synthesis of substance P, whereas interleukin-1α reduces the expression of these miRs, relieving their inhibition. [score:7]
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73
[+] score: 7
More specifically, that study showed that miR-19a, miR-101, and miR-130a co-regulate the 3′-UTR of ATXN1 through the inhibition of ATXN1 translation [48]. [score:6]
Interestingly, miR-101 affected both the mRNA and protein levels, whereas miR-19a and miR-130a decreased the protein levels only. [score:1]
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74
[+] score: 6
Five miRNAs (hsa-miR-130a*, hsa-miR-296-5p, hsa-miR-493*, hsa-miR-520d-3p, hsa-miR-661) had different expression levels between latent TB and healthy controls; all of them except hsa-miR-296-5p were up-regulated in healthy controls. [score:6]
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75
[+] score: 6
Indeed, the phenomenon of various expression differences could be detected according to more miRNAs: the most abundant isomiR of miR-130a was over 29.60-fold than the secondary abundant isomiR (Figure 6A), while similar expression levels (over 1.17-fold) could be found between the most and secondary abundant isomiRs of miR-451 (Figure 6D). [score:5]
For example, in mild sample, miR-451 was found 10 variants (sequence counts of them were over 99), while miR-130a was only found 2 variants (Figure 5 and Figure 6). [score:1]
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76
[+] score: 6
However, the related family members miR-130a and miR-130b (that is, with the same seed regions as miR-301a and likely overlapping targets) both increased basal reporter activity by 4.5-fold (P = 0.04) and 3.6-fold (P = 0.06), respectively (see Additional file 1, Table S2). [score:3]
Hence, our results are in agreement with the Lu et al. study suggesting that the miR-301/miR-130 family positively regulates NF-κB signaling. [score:2]
Further, miR-130a was a hit in the +TNF screen with a 3.8-fold increase (P = 0.02; Table 1). [score:1]
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77
[+] score: 6
A direct role of miR-130a in inhibition of Smad4 synthesis has been demonstrated in neutrophil precursors [24] and the repression of Smad4 mRNA by miR-146a has likewise been demonstrated in the acute promyelocytic leukemia cell line NB4 [25]. [score:4]
The miRNAs were miR-130a and miR-155 (cluster 1), miR-146a (cluster 2), miR-34c-3p (cluster 3), miR-99b (cluster 4), miR-183 and miR-26a (cluster 5), and miR-27a and miR-223 (cluster 6). [score:1]
High levels of miR-130a, miR-155, and miR-146a were observed in MB/PMs. [score:1]
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78
[+] score: 6
A reproducible repression of endogenous BTG1 protein was also observed for vectors expressing miR-19b and miR-130, suggesting the possibility that multiple miRNAs target BTG1. [score:5]
These miRNAs included hsa-mir-130, hsa-mir-301a, hsa-mir-302, hsa-mir-454-3p, and hsa-mir-19b. [score:1]
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79
[+] score: 6
Later on, by assessing the differential expression of 84 miRNAs in the sera of severe endometriosis cases, we suggested that miR-130a may be EIF mediates the trans-differentiation of MSCs into endometrial-like cells, in addition to regulating gene expression in several endometriosis related biological processes and cell functions (Azmy and Elgarf, 2012[4]; Azmy et al., 2014[3]). [score:6]
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80
[+] 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]
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81
[+] score: 6
A distinct miRNA profiling was shown in the paclitaxel-resistant ovarian cancer, and particularly down-regulation of miR-130a was associated with the translational activation of the macrophage colony-stimulating factor (M-CSF) gene, a known resistance factor for ovarian cancer [100], possibly owing to the role of matrix metalloproteinases (MMPs) in the CSF-1 -mediated effect on tumour progression [101]. [score:6]
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82
[+] score: 6
Microarray analysis showed altered expression of some miRNAs in hepatomas such as let-7a, miR-21, miR-23, miR-130, whereas the hepato-specific miR-122a and others were found downregulated in 70% of HCCs and in HCC-derived cell lines [20], [46], [47], as reported in our data (Table 1). [score:6]
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83
[+] score: 6
Using the microarray approach we identified 58 differentially expressed miRNAs, including miR-21, miR-30b, miR-27a, miR-106b, miR-181a/b, miR-130a, let-7e, let-7b, let-7f, let-7g, let-7a and miR-34a, all of them up-regulated. [score:6]
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84
[+] score: 6
Hepatitis C virus infection modulates expression of interferon stimulatory gene IFITM1 by upregulating miR-130A. [score:6]
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85
[+] 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-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-20a, hsa-mir-22, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-98, hsa-mir-101-1, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-15b, mmu-mir-101a, mmu-mir-126a, mmu-mir-130a, mmu-mir-133a-1, mmu-mir-142a, mmu-mir-181a-2, mmu-mir-194-1, hsa-mir-208a, hsa-mir-30c-2, mmu-mir-122, mmu-mir-143, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-181a-1, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-122, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-142, hsa-mir-143, hsa-mir-126, hsa-mir-194-1, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-208a, 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-16-1, mmu-mir-16-2, mmu-mir-18a, mmu-mir-20a, mmu-mir-22, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-29c, mmu-mir-98, mmu-mir-326, rno-mir-326, rno-let-7d, rno-mir-20a, rno-mir-101b, mmu-mir-101b, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-17, mmu-mir-19a, mmu-mir-181a-1, mmu-mir-26a-2, mmu-mir-19b-1, mmu-mir-181b-1, mmu-mir-181c, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-101-2, hsa-mir-26a-2, hsa-mir-378a, mmu-mir-378a, hsa-mir-326, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-181b-2, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-15b, rno-mir-16, rno-mir-17-1, rno-mir-18a, rno-mir-19b-1, rno-mir-19a, rno-mir-22, rno-mir-26a, rno-mir-26b, rno-mir-29c-1, rno-mir-30c-1, rno-mir-30c-2, rno-mir-98, rno-mir-101a, rno-mir-122, rno-mir-126a, rno-mir-130a, rno-mir-133a, rno-mir-142, rno-mir-143, rno-mir-181c, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-194-1, rno-mir-194-2, rno-mir-208a, rno-mir-181a-1, hsa-mir-423, hsa-mir-18b, hsa-mir-20b, hsa-mir-451a, mmu-mir-451a, rno-mir-451, ssc-mir-122, ssc-mir-15b, ssc-mir-181b-2, ssc-mir-19a, ssc-mir-20a, ssc-mir-26a, ssc-mir-326, ssc-mir-181c, ssc-let-7c, ssc-let-7f-1, ssc-let-7i, ssc-mir-18a, ssc-mir-29c, ssc-mir-30c-2, hsa-mir-484, hsa-mir-181d, hsa-mir-499a, rno-mir-1, rno-mir-133b, mmu-mir-484, mmu-mir-20b, rno-mir-20b, rno-mir-378a, rno-mir-499, hsa-mir-378d-2, mmu-mir-423, mmu-mir-499, mmu-mir-181d, mmu-mir-18b, mmu-mir-208b, hsa-mir-208b, rno-mir-17-2, rno-mir-181d, rno-mir-423, rno-mir-484, mmu-mir-1b, ssc-mir-15a, ssc-mir-16-2, ssc-mir-16-1, ssc-mir-17, ssc-mir-130a, ssc-mir-101-1, ssc-mir-101-2, ssc-mir-133a-1, ssc-mir-1, ssc-mir-181a-1, ssc-let-7a-1, ssc-let-7e, ssc-let-7g, ssc-mir-378-1, ssc-mir-133b, ssc-mir-499, ssc-mir-143, ssc-mir-423, ssc-mir-181a-2, ssc-mir-181b-1, ssc-mir-181d, ssc-mir-98, ssc-mir-208b, ssc-mir-142, ssc-mir-19b-1, hsa-mir-378b, ssc-mir-22, rno-mir-126b, rno-mir-208b, rno-mir-133c, hsa-mir-378c, ssc-mir-194b, ssc-mir-133a-2, ssc-mir-484, ssc-mir-30c-1, ssc-mir-126, ssc-mir-378-2, ssc-mir-451, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, mmu-mir-378b, mmu-mir-101c, hsa-mir-451b, hsa-mir-499b, ssc-let-7a-2, ssc-mir-18b, hsa-mir-378j, rno-mir-378b, mmu-mir-133c, mmu-let-7j, mmu-mir-378c, mmu-mir-378d, mmu-mir-451b, ssc-let-7d, ssc-let-7f-2, ssc-mir-20b-1, ssc-mir-20b-2, ssc-mir-194a, mmu-let-7k, mmu-mir-126b, mmu-mir-142b, rno-let-7g, rno-mir-15a, ssc-mir-378b, rno-mir-29c-2, rno-mir-1b, ssc-mir-26b
let-7, miR-98, miR-130a and miR-16 showed uniform levels of expression in 13 different tissues but were hardly detected in pancreas (Figure 3A). [score:3]
Similarly, let-7, miR-98, miR-16 and miR-130a are abundantly expressed in 13 of the 14 tissues (except in pancreas) (Figure 3A). [score:3]
[1 to 20 of 2 sentences]
86
[+] 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-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-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-140, 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
In a review, Gramantieri et al. (2008) show miRNAs aberrantly expressed in HCC compared to non-tumorous liver tissue (up -expression of miR-33, miR-130, miR-135a, miR-210, miR-213, miR-222, miR-331, miR-373, miR-376a, and down -expression of miR-130a, miR-132, miR-136, miR-139, miR-143, miR-145, miR-150, miR-200a, miR-200b, miR-214). [score:6]
[1 to 20 of 1 sentences]
87
[+] score: 6
Several laboratories have shown that miRNAs directly inhibit EGFR or/and c-Met expression, such as miR-7, miR-146a, miR-574-3p, miR-34a, miR-130a and miR-1/206 (42– 47). [score:6]
[1 to 20 of 1 sentences]
88
[+] score: 6
One of the direct YAP targets, miR-130a, could strongly repress the inhibitory effect of VGLL4 on YAP, leading to the constitutive activation of YAP (Shen et al., 2015). [score:6]
[1 to 20 of 1 sentences]
89
[+] score: 5
For instance, miR-130a can repress the transcription of ATG5 and ATG16L, and Atg12 is a target of miR-454-3p. [score:3]
[109] As HOTAIR can interact with numerous miRNAs, such as miR-34a, miR-331-3P, miR-130a and miR-454-3p, we should recall that HOTAIR regulates autophagy in two ways. [score:2]
[1 to 20 of 2 sentences]
90
[+] score: 5
Specifically, in TNFα -treated adipocytes, miR-146b, miR-130 and miR-155 were upregulated. [score:4]
Several miRNAs, such as miR-132 [15], miR-155 [16], miR-130 [17], miR-145 [18], miR-146b [19], and miR-29 [20] have been indentified in obesity -associated inflammation and insulin-resistance in adipocytes. [score:1]
[1 to 20 of 2 sentences]
91
[+] score: 5
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-19b-2, hsa-mir-20a, hsa-mir-22, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-98, hsa-mir-99a, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-10a, hsa-mir-10b, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-181a-1, hsa-mir-221, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-27b, hsa-mir-30b, hsa-mir-152, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-185, hsa-mir-193a, hsa-mir-320a, hsa-mir-200c, hsa-mir-1-1, hsa-mir-181b-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-99b, hsa-mir-130b, hsa-mir-30e, hsa-mir-363, hsa-mir-374a, hsa-mir-375, hsa-mir-378a, hsa-mir-148b, hsa-mir-331, hsa-mir-339, hsa-mir-423, hsa-mir-20b, hsa-mir-491, hsa-mir-193b, hsa-mir-181d, hsa-mir-92b, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, bta-mir-29a, bta-let-7f-2, bta-mir-148a, bta-mir-18a, bta-mir-20a, bta-mir-221, bta-mir-27a, bta-mir-30d, bta-mir-320a-2, bta-mir-99a, bta-mir-181a-2, bta-mir-27b, bta-mir-30b, bta-mir-106a, bta-mir-10a, bta-mir-15b, bta-mir-181b-2, bta-mir-193a, bta-mir-20b, bta-mir-30e, bta-mir-92a-2, bta-mir-98, bta-let-7d, bta-mir-148b, bta-mir-17, bta-mir-181c, bta-mir-191, bta-mir-200c, bta-mir-22, bta-mir-29b-2, bta-mir-29c, bta-mir-423, bta-let-7g, bta-mir-10b, bta-mir-24-2, bta-mir-30a, bta-let-7a-1, bta-let-7f-1, bta-mir-30c, bta-let-7i, bta-mir-25, bta-mir-363, bta-let-7a-2, bta-let-7a-3, bta-let-7b, bta-let-7c, bta-let-7e, bta-mir-15a, bta-mir-19a, bta-mir-19b, bta-mir-331, bta-mir-374a, bta-mir-99b, hsa-mir-374b, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, bta-mir-1-2, bta-mir-1-1, bta-mir-130a, bta-mir-130b, bta-mir-152, bta-mir-181d, bta-mir-182, bta-mir-185, bta-mir-24-1, bta-mir-193b, bta-mir-29d, bta-mir-30f, bta-mir-339a, bta-mir-374b, bta-mir-375, bta-mir-378-1, bta-mir-491, bta-mir-92a-1, bta-mir-92b, bta-mir-9-1, bta-mir-9-2, bta-mir-29e, bta-mir-29b-1, bta-mir-181a-1, bta-mir-181b-1, bta-mir-320b, bta-mir-339b, bta-mir-19b-2, bta-mir-320a-1, bta-mir-193a-2, bta-mir-378-2, hsa-mir-378b, hsa-mir-320e, hsa-mir-378c, bta-mir-148c, hsa-mir-374c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-378j, bta-mir-378b, bta-mir-378c, bta-mir-378d, bta-mir-374c, bta-mir-148d
In addition, many miRNA families showed low expression (count number <100) in milk exosomes, such as the miR-1, miR-130, miR-17, miR-10, miR-29, miR-374, mir-9, miR-15 and miR-491 families (Figure 12F), which are routinely expressed in specific tissues [53– 56]. [score:5]
[1 to 20 of 1 sentences]
92
[+] score: 5
Other miRNAs from this paper: hsa-mir-16-1, hsa-mir-17, hsa-mir-20a, hsa-mir-21, hsa-mir-23a, hsa-mir-100, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-107, hsa-mir-16-2, mmu-mir-1a-1, mmu-mir-23b, mmu-mir-125b-2, mmu-mir-130a, mmu-mir-9-2, mmu-mir-145a, mmu-mir-181a-2, mmu-mir-184, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-205, mmu-mir-206, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-199a-2, hsa-mir-205, hsa-mir-181a-1, hsa-mir-214, hsa-mir-219a-1, hsa-mir-223, mmu-mir-302a, hsa-mir-1-2, hsa-mir-23b, hsa-mir-125b-1, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-184, hsa-mir-206, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-20a, mmu-mir-21a, mmu-mir-23a, mmu-mir-103-1, mmu-mir-103-2, rno-mir-338, mmu-mir-338, rno-mir-20a, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-107, mmu-mir-17, mmu-mir-100, mmu-mir-181a-1, mmu-mir-214, mmu-mir-219a-1, mmu-mir-223, mmu-mir-199a-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-181b-1, mmu-mir-125b-1, hsa-mir-302a, hsa-mir-219a-2, mmu-mir-219a-2, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-367, hsa-mir-372, hsa-mir-338, mmu-mir-181b-2, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-16, rno-mir-17-1, rno-mir-21, rno-mir-23a, rno-mir-23b, rno-mir-100, rno-mir-103-2, rno-mir-103-1, rno-mir-107, rno-mir-125b-1, rno-mir-125b-2, rno-mir-130a, rno-mir-145, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-184, rno-mir-199a, rno-mir-205, rno-mir-206, rno-mir-181a-1, rno-mir-214, rno-mir-219a-1, rno-mir-219a-2, rno-mir-223, hsa-mir-512-1, hsa-mir-512-2, rno-mir-1, mmu-mir-367, mmu-mir-302b, mmu-mir-302c, mmu-mir-302d, rno-mir-17-2, hsa-mir-1183, mmu-mir-1b, hsa-mir-302e, hsa-mir-302f, hsa-mir-103b-1, hsa-mir-103b-2, rno-mir-9b-3, rno-mir-9b-1, rno-mir-9b-2, rno-mir-219b, hsa-mir-23c, hsa-mir-219b, mmu-mir-145b, mmu-mir-21b, mmu-mir-21c, mmu-mir-219b, mmu-mir-219c, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
From the top twenty miRNAs showing highest expression in A2B5+ GalC− cells, miR-130a, miR-16, miR-17, and miR-20a were also in the top twenty expressed miRNAs from our GPs. [score:5]
[1 to 20 of 1 sentences]
93
[+] score: 5
A group of 39 miRNAs was significantly down-regulated by Nkx2-1 knock-down including miR-1195 (−4.9 fold), miR-378 (−4.6 fold), miR-449a (−2.1 fold), and miR-130a (−1.9 fold) (Figure  2A and Table  1). [score:5]
[1 to 20 of 1 sentences]
94
[+] score: 5
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-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26b, hsa-mir-27a, hsa-mir-31, hsa-mir-33a, hsa-mir-99a, hsa-mir-100, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-147a, hsa-mir-34a, hsa-mir-182, hsa-mir-199a-2, hsa-mir-212, hsa-mir-221, hsa-mir-224, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-132, hsa-mir-142, hsa-mir-145, hsa-mir-152, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-127, hsa-mir-134, hsa-mir-200c, hsa-mir-106b, hsa-mir-361, hsa-mir-148b, hsa-mir-20b, hsa-mir-410, hsa-mir-202, hsa-mir-503, hsa-mir-33b, hsa-mir-643, hsa-mir-659, bta-let-7f-2, bta-mir-103-1, bta-mir-148a, bta-mir-21, bta-mir-221, bta-mir-26b, bta-mir-27a, bta-mir-99a, bta-mir-125a, bta-mir-125b-1, bta-mir-145, bta-mir-199a-1, bta-mir-27b, bta-mir-30b, bta-mir-31, bta-mir-127, bta-mir-142, bta-mir-20b, bta-let-7d, bta-mir-132, bta-mir-148b, bta-mir-200c, bta-mir-22, bta-mir-23a, bta-mir-29b-2, bta-mir-361, bta-let-7g, bta-mir-24-2, bta-let-7a-1, bta-let-7f-1, bta-let-7i, bta-mir-25, bta-let-7a-2, bta-let-7a-3, bta-let-7b, bta-let-7c, bta-let-7e, bta-mir-103-2, bta-mir-125b-2, bta-mir-34a, hsa-mir-708, hsa-mir-147b, hsa-mir-877, hsa-mir-940, hsa-mir-548j, hsa-mir-302e, hsa-mir-103b-1, hsa-mir-103b-2, bta-mir-100, bta-mir-106b, bta-mir-130a, bta-mir-134, bta-mir-147, bta-mir-152, bta-mir-153-1, bta-mir-153-2, bta-mir-182, bta-mir-24-1, bta-mir-199a-2, bta-mir-202, bta-mir-212, bta-mir-224, bta-mir-33a, bta-mir-33b, bta-mir-410, bta-mir-708, bta-mir-877, bta-mir-940, bta-mir-29b-1, bta-mir-148c, bta-mir-503, bta-mir-148d
This study demonstrated that eight miRNAs (miR-503, miR-21, miR-29b, miR-142-3p, miR-34a, miR-152, miR-25 and miR-130a) were highly expressed, while nine miRNAs (miR-125a, miR-199a-3p, miR-125b, miR-99a, let-7c, miR-145, miR-31, miR-202 and miR-27b) were expressed at lower level between the follicular and luteal stages in ovine ovarian tissues. [score:5]
[1 to 20 of 1 sentences]
95
[+] score: 5
microRNA-103 represses the expression of TIMP-3 [27] (elevated 8.7 fold in neonatal CPCs, p = 0.0027) and microRNA-130a represses the expression of HOXA5 [50] (elevated 2.4 fold in neonatal CPCs, p = 0.0288). [score:5]
[1 to 20 of 1 sentences]
96
[+] score: 5
Yoon et al. [8] found that MS2 -mediated pulldown of lincRNA-p21 could identify interacting target miRNAs with functional impact on the expression of lincRNA-p21, and at least four miRNAs (miR-130, miR-221, let-7b, let-7c) were enriched in the lincRNA-p21-MS2 pulldown. [score:5]
[1 to 20 of 1 sentences]
97
[+] score: 5
miR-130a +Expression of miR-130a was significantly up-regulated in primary glioblastomas compared with normal peripheral brain tissue [44]. [score:5]
[1 to 20 of 1 sentences]
98
[+] score: 5
McBride et al. (2012) observed nine miRNAs (miR-125a, miR-199a-3p, miR-125b, miR-99a, let-7c, miR-145, miR-31, miR-202 and miR-27b) with decreased expression and eight miRNAs (miR-503, miR-21, miR-29b, miR-142-3p, miR-34a, miR-152, miR-25 and miR-130a) with increased expression between the follicular and luteal stages in ovine ovarian tissues [21]. [score:5]
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99
[+] score: 5
miR-25, miR-93, miR-106b, and miR-130 inhibit apoptosis by preventing the expression of the pro-apoptotic protein, Bim (Figure 2) [14]. [score:5]
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100
[+] score: 5
Turini Gonzales Marioto et al. (97) evaluated the miRNA profiles in mice intravenously administered P. brasiliensis and showed that the most upregulated miRNAs at 28 days included miR-126a-5p, miR-340-5p, miR-30b-5p, miR-19b-3p, miR-221-3p, miR-20a-5p, miR-130a-3p, and miR-301a-3p, whereas after 56 days, miRNAs from the let-7 family, as well as miR-26b-5p, and miR-369-3p were the greatest upregulated miRNAs (97). [score:5]
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