sort by

29 publications mentioning mmu-mir-215

Open access articles that are associated with the species Mus musculus and mention the gene name mir-215. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 336
Other miRNAs from this paper: mmu-mir-192, mmu-mir-224
In addition, western blot analyses proved that overexpression of miR-215-5p suppresses the expression of both proteins 48 h after transfection (Fig.   4g). [score:7]
Cell counting demonstrated cell proliferation to be inhibited by ectopic expression of miR-215-5p, with the best inhibition effect being observed 96 h after transfection (P < 0.001 for HCT-116 [+/+] and HT-29; P < 0.01 for DLD-1 and HCT-116 [−/−]; Figs.   2a, b, Supplementary Figs.   S2A, B). [score:7]
e Involvement of miR-215-5p in CRC pathogenesis—direct targets of miR-215-5p described first in this study are in red squares, direct targets of miR-215-5p described in previous studies are in brown. [score:7]
As in the Czech cohort, the expression of miR-215-5p was significantly downregulated in tumor tissues (P < 0.0001; Fig.   1b) and its low levels were associated with advanced clinical stage (P = 0.0185; Fig.   1d), but not with the lymph node positivity (Table  1). [score:6]
Hou Y miR-215 functions as a tumor suppressor and directly targets ZEB2 in human non-small cell lung cancerOncol. [score:6]
In this study, we have determined expression levels of miR-215-5p in two large independent cohorts of CRC patients to confirm its downregulation in tumor tissue and prognostic potential. [score:6]
Ge G miR-215 functions as a tumor suppressor in epithelial ovarian cancer through regulation of the X-chromosome-linked inhibitor of apoptosisOncol. [score:6]
Georges et al. confirmed denticleless protein homolog to be a direct target of miR-215-5p that interacts with DDB1-CUL4 and MDM2-p53 ligase complexes and influences the stability of p53 and its target p21 31, 32. [score:6]
We focus on miR-215-5p as we identified this miRNA to be downregulated in colorectal tumor tissue in our previous work [11], where it indicated also promising tumor-suppressive features in preliminary in vitro functional screen [11]. [score:6]
MiR-215-5p overexpression suppresses tumor growth in vivoTo evaluate how miR-215-5p overexpression affects tumor growth in vivo, subcutaneous tumors were generated in NSG mice using HCT-116 [+/+]-miR-215-5p cells and HCT-116 [+/+]-control cells. [score:5]
We successfully silenced miR-215-5p expression in CaCo2 cells to 16% of its expression levels in control CaCo2 cells transfected with anti-miRNA control oligonucleotide (Supplementary Fig.   S8A). [score:5]
Importantly, reverse transcriptase-quantitative PCR (RT-qPCR) analysis showed that the expression of miR-215-5p is still upregulated in HCT-116 [+/+]-miR-215-5p tumors compared with control tumors (Fig.   5d) 25 days from the beginning of the experiment. [score:5]
We have confirmed that the expression of miR-215-5p is significantly downregulated in tumor tissues compared with paired healthy tissues and its reduced levels correlate with higher clinical stage, presence of lymph node metastases and shorter OS. [score:5]
Fig. 2Effects of miR-215-5p overexpression on HCT-116 [+/+] and DLD-1 cells a miR-215-5p significantly inhibits the proliferation of HCT-116 [+/+] cells. [score:5]
Silencing of miR-215-5p by use of anti-miR-215 in CaCo2 cells led to the increase in expression levels of miR-215-5p targets EREG and HOXB9 after 48 h (Supplementary Fig.   S8B). [score:5]
The average expression levels of miR-215-5p in tumor and adjacent non-tumor tissues, as well as in the cell lines were normalized using RNU48 as a reference gene, the expression of EREG and HOXB9 was normalized using PMM1 (in case of tissue samples) or GAPDH (in case of cell lines) as a reference genes; subsequently, all data were transformed by the 2 [−ΔCt] method. [score:5]
All cell lines were transfected with 10 nM hsa-miR-215-5p mimic (MC10874) or miRNA Mimic, negative control #1 (4464058) or 33 nM hsa-miR-215-5p inhibitor (MH10874) or 33 nM miRNA inhibitor, negative control (4464079) or 30 nM siRNA -negative control (AM4635), siEREG (145900) and siHOXB9 (109525; all from Ambion) 24 h after seeding using Lipofectamine RNAiMAX transfection reagent (Invitrogen) according to the manufacturer’s protocol. [score:5]
Li QW MicroRNA-215 functions as a tumor suppressor and directly targets ZEB2 in human pancreatic cancerGenet. [score:5]
It was confirmed that the expression of miR-215-5p is significantly downregulated in tumor tissue compared with adjacent mucosa (P < 0.0001; Fig.   1a) in case of Czech cohort (Table  1). [score:5]
MiR-215-5p is downregulated in CRC tissues and its low levels correlate with aggressive disease. [score:5]
To date, no previous study has confirmed EREG and HOXB9 to be direct targets of miR-215-5p. [score:4]
The performed analyses proved these two proteins to be the direct targets of miR-215-5p. [score:4]
It was shown that miR-215-5p suppressed 62 ± 6% of reporter activity of the pEZX-MT05-EREG reporter compared with the control oligonucleotide, whereas the pEZX-MT05-ctrl vector was resistant to the inhibition (P < 0.001; Fig.   4e). [score:4]
Further, significantly downregulated levels of miR-215-5p were found not only in primary tumors, but also in corresponding liver metastases (P < 0.0001; Supplementary Fig.   S1B). [score:4]
f confirmed HOXB9 to be a direct target of miR-215-5p. [score:4]
g Western blot analyses proved downregulated protein levels of EREG and HOXB9 in CRC cells transfected with miR-215-5p mimics. [score:4]
Over the past decade, several miRNAs with deregulated expression in CRC have been identified, including miR-215-5p 11– 15. [score:4]
In 2011, White et al. identified ZEB2 as a direct target of miR-215-5p in renal cell carcinoma [37]. [score:4]
MiR-215-5p overexpression suppresses tumor growth in vivo. [score:4]
However, Wu et al. identified HOXB9 as a direct target of miR-192, a miRNA from the same family and with a high homology to miR-215-5p [43]. [score:4]
Using the metastatic gene profiling assay, several other genes involved in the degradation of extracellular matrix or cell adhesion, such as MMP7/13 or CDH1/6/11, have been described to be affected by increased miR-215-5p expression in renal cell carcinoma [37]; however, these targets need to be further validated in CRC. [score:4]
e confirmed EREG to be a direct target of miR-215-5p. [score:4]
EREG and HOXB9 are direct targets of miR-215-5p. [score:4]
Similarly, the reporter activity of the pLSG-RenSP-HOXB9 reporter was suppressed by 48 ± 3% after transfection of miR-215-5p compared with control cells, whereas the pLSG-RenSP-ctrl vector was resistant to the inhibition (P < 0.001; Fig.   4f). [score:4]
Effects of miR-215-5p overexpression on HCT-116 [+/+] and DLD-1 cells. [score:3]
b miR-215-5p significantly inhibits the proliferation of DLD-1 cells. [score:3]
Effects of miR-215-5p overexpression on tumor growth in vivo and its involvement in CRC pathogenesis. [score:3]
Low expression levels of miR-215-5p were associated with resistance to 5-fluorouracil-containing adjuvant chemotherapy [16]. [score:3]
Finally, the deregulation of this miRNA is supposed to be a very early event, which is not dependent on the mechanism of initiation of transformation, suggesting that miR-215-5p is likely to regulate critical signaling pathways that are crucial for early transformation of colonic epithelial cells [12]. [score:3]
Expression analyses of miR-215-5p in CRC patients. [score:3]
Effects of miR-215-5p overexpression on migration of HCT-116 [+/+] and DLD-1 cells. [score:3]
To further discover the role of miR-215-5p in CRC pathogenesis, we have performed deep in vitro analyses with the aim to describe the most significantly affected CRC cells phenotypes and identify mRNA targets and the key signaling pathways affected by miR-215-5p. [score:3]
Similarly, Boni et al. identified thymidylate synthase as another target of miR-215-5p that was suggested to be a predictive biomarker for 5-FU response in CRC. [score:3]
Furthermore, Mann–Whitney U-test was used to analyze the correlation between miR-215-5p expression levels and clinical–pathological features of the patients. [score:3]
Georges et al. identified discs large homolog 5 as an important target of miR-215-5p [31]. [score:3]
Concerning the effect of miR-215-5p on cell apoptosis, it was assessed that overexpression of this miRNA leads to the significant increase of apoptotic rate in case of HCT-116 [+/+] cells. [score:3]
Generation of stable cell line overexpressing miR-215-5p. [score:3]
Thus, we believe that miR-215-5p could serve as a potential therapeutic target in CRC. [score:3]
To date, no target genes of miR-215-5p associated with cell apoptosis have been identified in CRC. [score:3]
In 2008, miR-215-5p was first described as a tumor suppressor in CRC [13]. [score:3]
In addition, we have proved the tumor-suppressive character of miR-215-5p resulting in reduced proliferation, formation of new colonies, and migration and increased apoptosis. [score:3]
To find out whether the inhibition of growth induced by miR-215-5p was anchorage independent, the cells were seeded on soft agar 24 h post-transfection. [score:3]
e Overexpression of miR-215-5p in HCT-116 [+/+] cells leads to a cell cycle arrest in G2/M phase. [score:3]
c Expression of miR-215-5p significantly decreases with advanced clinical stage (P < 0.0001; Czech cohort). [score:3]
In addition, the levels of miR-215-5p decreased progressively with advanced clinical stages (P < 0.0001; Fig.   1c) and low expression was associated with lymph nodes positivity (P < 0.0001; Supplementary Fig.   S1A). [score:3]
d Expression of miR-215-5p significantly decreases with advanced clinical stage (P = 0.0185; Spain cohort). [score:3]
Further, denticleless protein homolog [14] and thymidylate synthase [15] were confirmed to be the miR-215-5p targets. [score:3]
f Overexpression of miR-215-5p in DLD-1 cells leads to a cell cycle arrest in G2/M phase. [score:3]
As our observations proved significant effects of miR-215-5p on cell proliferation and migration, several databases have been searched for the potential targets of miR-215-5p associated with these processes. [score:3]
Thus, we have analyzed not only the diagnostic and prognostic potential of miR-215-5p, but we also aimed to identify its target genes and describe its involvement in CRC cells phenotypes and particular signaling pathways. [score:3]
Since then, several other authors studied prognostic and predictive value of miR-215-5p 14– 16; however, its detail functioning in the pathogenesis of the disease has not been clarified yet. [score:3]
Further, we observed that higher levels of miR-215-5p lead to a significant inhibition of cell migration. [score:3]
In total, 252 tumor tissue samples from patients with histopathologically verified CRC who had undergone surgery at Masaryk Memorial Cancer Institute (Brno, Czech Republic) from 2004 to 2013, as well as 252 paired adjacent non-tumor tissues were used for the determination of miR-215-5p expression levels. [score:3]
MiR-215-5p inhibits proliferation, viability and colony formation of CRC cells. [score:2]
The inhibition rate was 57 ± 16%, 37 ± 8%, and 50 ± 17%, respectively, in HCT-116 [+/+] (Fig.   3c), DLD-1 (Fig.   3d), and HCT-116 [−/−] cells transfected with miR-215-5p mimics compared with control group. [score:2]
As miR-215-5p has an ability to regulate EGFR ligand EREG and its transcriptional inducer HOXB9, we suggest that the main molecular link between miR-215-5p and CRC cells phenotypes presents the EGFR signaling pathway, which is one of the canonical pathogenic pathways in CRC (Fig.   5e). [score:2]
Fig. 1 a Expression levels of miR-215-5p are significantly decreased in CRC tissues compared with healthy adjacent tissues (P < 0.0001; Czech cohort). [score:2]
MiR-215-5p expression levels in CRC cells used in our study was performed by use of calibration curve (Supplementary Fig.   S7A) and absolute quantification. [score:2]
a Expression levels of miR-215-5p are significantly decreased in CRC tissues compared with healthy adjacent tissues (P < 0.0001; Czech cohort). [score:2]
MiR-215-5p silencing facilitate proliferation of CRC cells and induce expression of EREG and HOXB9. [score:2]
The most prominent regulatory effect of miR-215-1p on HOXB9 was observed under p53-wild-type conditions, in cell line HCT-116 [+/+], which could be partly explained by the fact that miR-192 13, 44 and miR-215 [44] have been shown to be p53-responsive miRNAs. [score:2]
By transfection of miR-215-5p, mimic reached significant increase of miR-215-5p levels in all studied cell lines, which was stable from 24 to 96 h. Expression levels of miR-215-5p in cells transfected with miR-215-5p mimic were 8000–10 000 times higher when compared with mock -transfected control cells. [score:2]
Li S MicroRNA-215 inhibits relapse of colorectal cancer patients following radical surgeryMed. [score:2]
Survival analyses proved that patients with low levels of miR-215-5p have significantly shorter overall survival (OS) (P = 0.0024; cut-off 0.02393; Fig.   1e) compared with patients with higher expression levels. [score:2]
MiR-215-5p expression levels in CRC cells. [score:2]
Fig. 3Effects of miR-215-5p overexpression on migration of HCT-116 [+/+] and DLD-1 cells a miR-215-5p significantly reduce the migration of HCT-116 [+/+] cells (transwell migration assay). [score:2]
d Expression levels of miR-215-5p were significantly increased in HCT-116 [+/+]-miR-215-5p tumors compared with HCT-116 [+/+]-control tumors 25 days after initiation of the experiment. [score:2]
Fig. 5Effects of miR-215-5p overexpression on tumor growth in vivo and its involvement in CRC pathogenesis a Subcutaneously injected HCT-116 [+/+]-miR-215-5p cells formed significantly smaller tumors compared with HCT-116 [+/+]-control cells 25 days after application into NSG mice (n = 5). [score:2]
According to the results of scratch wound assay, transfection of miR-215-5p mimics led to a significant inhibition of cell migration (P < 0.001 for DLD-1, HCT-116 [+/+] and HCT-116 [−/−]; P < 0.05 for HT-29; Figs.   3a, b and Supplementary Figs.   S3A, B). [score:2]
MiR-215-5p inhibits migration of CRC cells. [score:2]
MiR-215-5p levels in CRC cells were expressed as number of copies per 100 ng of total RNA purified from CRC cells. [score:2]
Boni V miR-192/miR-215 influence 5-fluorouracil resistance through cell cycle -mediated mechanisms complementary to its post-transcriptional thymidilate synthase regulationMol. [score:2]
In 2008, miR-215 has been shown to act as an effector as well as regulator of p53 [13]. [score:2]
MiR-215 induces increase in E-cadherin expression. [score:2]
To find out whether the inhibition of growth induced by miR-215-5p was anchorage independent, the clonogenic assay was performed [15]. [score:2]
In addition, transwell migration assay confirmed significantly reduced migration of cells overexpressing miR-215-5p. [score:2]
b Expression levels of miR-215-5p are significantly decreased in CRC tissues compared with healthy adjacent tissues (P < 0.0001; Spain cohort). [score:2]
It was found that miR-215-5p transfection leads to the significant decrease in mRNA levels of both genes of interest (Figs.   4a-d). [score:1]
The number of miR-215-5p copies varied among CRC cells (Supplementary Fig.   S7B). [score:1]
e Low levels of miR-215-5p correlate with shorter OS of Czech CRC patients (P = 0.0024). [score:1]
It was revealed that number of colonies is significantly lower in case of HCT-116 [+/+] and DLD-1 cells transfected with miR-215-5p mimics, but not in HCT-116 [−/−] and HT-29 cells indicating that this miRNA could affect the cell clone formation by mechanisms that are at least in part dependent on p53 functionality. [score:1]
Importantly, transfection of miR-215-5p mimics into HCT-116 [−/−] (p53 -null), DLD-1 (mut-p53) and HT-29 (mut-p53) cells did not lead to increased apoptosis rates and elevated levels of cleaved PARP (Fig.   2h, Supplementary Figs.   S2E–F). [score:1]
Concerning the cell cycle, transfection of miR-215-5p lead to the significant arrest in G2/M phase. [score:1]
After 14 days, HCT-116 [+/+] and DLD-1 cells transfected with miR-215-5p mimics formed significantly fewer colonies than cells transfected with control oligonucleotide (P < 0.001; Figs.   2e, f). [score:1]
In conclusion, we have confirmed a diagnostic and prognostic potential of miR-215-5p in CRC patients in two independent cohorts of patients. [score:1]
Although some of these effects were dependent on the presence of wt-p53, miR-215-5p was also able to slow down the tumor growth independently of this protein. [score:1]
g miR-215-5p increases the apoptosis of HCT-116 [+/+] cells in p53 -dependent manner. [score:1]
For quantification of the number of miR-215-5p copies in CRC cells used in our study, a dilution series of synthetic miRNA oligo (IDT, Coralville, IA, USA) were carried out in parallel with qRT-PCR of biological samples to generate an absolute standard curve. [score:1]
The results proved that higher levels of miR-215-5p significantly reduce metabolic activity and proliferation of CRC cell lines. [score:1]
Again, the low levels of miR-215-5p were associated with shorter OS and worse prognosis of CRC patients (P = 0.0111; cut-off 0.2139; Fig.   1f). [score:1]
Based on this results, HCT-116 [+/+], HCT-116 [−/−], DLD-1 and HT-29 cells were used as mo dels for miR-215-5p substitution and CaCo2 for miR-215-5p silencing. [score:1]
d miR-215-5p significantly reduce the clonogenicity of DLD-1 cells. [score:1]
Karaayvaz M Prognostic significance of miR-215 in colon cancerClin. [score:1]
Further, the levels of cleaved PARP were increased subsequent to transfection with miR-215-5p (Fig.   2g). [score:1]
h miR-215-5p increases the early apoptosis of DLD-1 cells. [score:1]
Stable transfectants were generated using OriGene’s pCMV6-Mir vectors with miR-215-5p precursor or control sequence and TurboFectin 8.0 (OriGene Technologies, Rockville, MD, USA). [score:1]
It was confirmed that HCT-116 [+/+]-control tumors grow significantly faster than the HCT-116 [+/+]-miR-215-5p tumors (Figs.   5a–c). [score:1]
On the other hand, miR-215-5p significantly reduced cell proliferation even in the absence of p53; thus it seems that this miRNA slows down the proliferation not only through the cell cycle arrest, but also by affecting another signaling pathways independent of p53 function. [score:1]
The stable expression of miR-215-5p was evaluated by RT-qPCR. [score:1]
Finally, decreased levels of miR-215-5p facilitated proliferation of CaCo2 cells, which was significant at first (P = 0.03) and second day (P = 0.02) post-transfection (Supplementary Fig.   S8C). [score:1]
For miRNA expression analyses, complementary DNA (cDNA) was synthesized from 10 ng of total RNA using gene-specific primers (has-miR-215-5p; ID 000518, RNU48; ID 001006) according to the TaqMan MicroRNA Assay protocol (Applied Biosystems, Foster City, CA, USA) and real-time PCR was performed using TaqMan Universal PCR Master Mix, NoUmpErase UNG (Applied Biosystems) as described previously [11]. [score:1]
To evaluate how miR-215-5p overexpression affects tumor growth in vivo, subcutaneous tumors were generated in NSG mice using HCT-116 [+/+]-miR-215-5p cells and HCT-116 [+/+]-control cells. [score:1]
Subsequently, the luciferase reporter assay was utilized to confirm direct interaction between miR-215-5p and 3′-UTR of EREG and HOXB9. [score:1]
Song B Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cellsMol. [score:1]
Interestingly, although carrying out the above experiments significant morphologic changes in HCT-116 [+/+] cells transfected with miR-215-5p, such as round shape and plate surface detachment, have been repeatedly observed. [score:1]
was performed using six-well plates pre-coated with 0.75% agarose as the bottom layer, whereas the top layer consisted of 0.35% agarose and tumor cells transfected with miR-215 mimics or control oligonucleotide. [score:1]
f Low levels of miR-215-5p correlate with shorter OS of Spain CRC patients (P = 0.0111). [score:1]
To identify specific cellular processes influenced by miR-215-5p, series of in vitro experiments have been performed. [score:1]
The opposite effects were observed when miR-215-5p silencing approach was used in CaCo2 cells, where decreased levels of miR-215-5p led to enhanced cellular proliferation. [score:1]
c miR-215-5p significantly reduce the clonogenicity of HCT-116 [+/+] cells. [score:1]
[1 to 20 of 120 sentences]
2
[+] score: 284
However, this upregulation was significantly inhibited by pretreatment with a specific miR-215 inhibitor. [score:8]
These results indicate that miR-215 promotes β-catenin activation and upregulates α-SMA and fibronectin expression in TGF-β1 -treated MMCs by targeting CTNNBIP1. [score:8]
In addition, in vivo miR-215 knockdown with antagomir-215 normalized CTNNBIP expression and inhibited Wnt/β-catenin signaling and expression of downstream genes α-SMA and fibronectin in the db/db mouse kidney. [score:8]
control, MMCs treated with control vectors; CTNNBIP1, MMCs treated with CTNNBIP1 expression vectors; mimic, miR-215 mimic; inhibitor, miR-215 inhibitor. [score:7]
Importantly, when TGF-β1 -treated MMCs were co -transfected with the miR-215 inhibitor in combination with CTNNBIP1 siRNA, the miR-215 inhibitor -mediated repression of α-SMA and fibronectin expression were largely abolished (Figs. 5B–E). [score:7]
These results further demonstrate that TGF-β1 downregulates CTNNBIP1 protein expression through an miR-215-regulated pathway. [score:7]
Importantly, our in vivo study demonstrated that antagonizing miR-215 expression in db/db mice significantly enhances endogenous CTNNBIP1 protein expression, resulting in reduced Wnt/β-catenin signaling and expression of downstream genes α-SMA and fibronectin, which is in agreement with the in vitro data. [score:7]
Thus, we used antagomir-215 to knock down miR-215 expression in db/db mice and further examine the effects of miR-215 inhibition on the CTNNBIP1/β-catenin pathway (Fig. 7A). [score:6]
In contrast, the miR-215 inhibitor markedly upregulated CTNNBIP1 protein levels. [score:6]
These results further suggest that in MMCs, CTNNBIP1 negatively regulates α-SMA and fibronectin expression by activating β-catenin, which may participate in miR-215 -mediated phenotypic transition and TGF-β1 -induced fibronectin expression (Fig. 6G). [score:6]
These results are consistent with our observations in vitro and suggest that miR-215 directly targets endogenous CTNNBIP1, which inhibits Wnt/β-catenin signaling and its downstream genes α-SMA and fibronectin in db/db mice in vivo. [score:6]
Furthermore, we noticed that both TGF-β1 and CTNNBIP1 siRNA increased α-SMA and fibronectin expression in MMCs, whereas a specific miR-215 inhibitor significantly reduced this TGF-β1 -induced effect. [score:5]
a, untreated MMCs; b-e, MMCs treated with CTNNBIP1 siRNA, TGF-β1 alone, TGF-β1 plus miR-215 inhibitor, or TGF-β1 plus miR-215 inhibitor plus CTNNBIP1 siRNA, respectively. [score:5]
Taken together, our findings strongly indicate that miR-192 and miR-215 were upregulated under diabetic conditions both in vitro and in vivo and that miR-192 and miR-215 may be critical regulators of TGF-β1 signaling, which accelerates the MC phenotypic transition. [score:5]
As shown in Figs. 3E and F, CTNNBIP1 protein expression was downregulated in MMCs that were transfected with the miR-215 mimic compared with the control group. [score:5]
Furthermore, MMCs displayed a typical spindle shape that is associated with increased α-SMA expression after TGF-β1 treatment; however, these phenotypic and morphological changes were reversed when cells were exposed to TGF-β1 and miR-215 inhibitor in combination for 24 hours (Fig. 4E). [score:5]
miR-215 expression was determined by qRT-PCR (B) and subsequently analyzed for CTNNBIP1 mRNA (C) and protein (D) expression levels in glomeruli from antagomir-215 -treated mice by qRT-PCR and immunohistochemical staining, respectively. [score:5]
Our results also demonstrate that transcriptionally active β-catenin induces α-SMA expression, which is indicative of MC activation and is accompanied by increased fibronectin expression in MMCs that are transfected with CTNNBIP1 siRNA and/or an miR-215 mimic. [score:5]
As shown in Fig. 3G, the miR-215 mimic significantly inhibited CTNNBIP1 3’-UTR luciferase activity by 90% relative to the negative miR-control but did not inhibit the two control constructs without the 3’-UTR (first pair of bars) or the Mut-CTNNBIP1 3’-UTR (third pair of bars). [score:5]
In vivo miR-215 inhibition reduces α-SMA and fibronectin expression. [score:5]
As shown in Figs. 7C, D and E, glomerular CTNNBIP1 expression in antagomir-215 -treated mice was markedly increased at both the mRNA and protein levels compared with the control mice, suggesting that miR-215 regulates CTNNBIP1 expression in vivo. [score:5]
Recently, miRNA expression profiles [19] revealed that several miRNAs (miR-192, miR-194, miR-204, miR-215, and miR-216) are highly and nearly exclusively expressed in the kidney. [score:5]
In vivo miR-215 knockdown reduces α-SMA and fibronectin expression in db/db mice. [score:4]
Additionally, using both gain- and loss-of-function experiments, we determined that only miR-215 regulated endogenous CTNNBIP1 expression ex vivo. [score:4]
Taken together, our findings demonstrate that miR-215 plays an essential role in diabetic nephropathy pathogenesis by regulating the CTNNBIP1/β-catenin pathway and further suggest that miR-215 is a potential therapeutic target for diabetic nephropathy. [score:4]
We found that miR-215 is a positive regulator of Wnt/β-catenin signaling, which appears to be critical in TGF-β1 -induced MC phenotypic transition specifically by suppressing CTNNBIP1. [score:4]
Magnification, ×200 in E. Our findings confirm that, in response to TGF-β1, miR-215 negatively regulates the CTNNBIP1 gene by targeting its 3’-UTR sequence. [score:4]
These observations led us to conclude that the miR-215/CTNNBIP1 pathway acts downstream of TGF-β1 signaling and functionally mediates MC activation and fibronectin expression by regulating the Wnt/β-catenin signaling pathway in diabetes. [score:4]
CTNNBIP1 is a direct target gene of miR-215. [score:4]
TGF-β1 induces MC phenotypic transition by regulating miR-215 expression. [score:4]
To evaluate the in vivo relevance of miR-215 knockdown to CTNNBIP1 expression, we analyzed CTNNBIP1 expression changes by qRT-PCR and immunohistochemical staining. [score:4]
Based on the above observations, we speculated that miR-215 promoted TGF-β1 -induced MC injury in DN via its target gene CTNNBIP1 and the Wnt/β-catenin pathway. [score:3]
Taken together, these results demonstrate a significant role for miR-215 in diabetic kidney disease. [score:3]
Next, we further verified whether CTNNBIP1 is a direct miR-215 target using luciferase reporter assays. [score:3]
CTNNBIP1 is a bona fide miR-215, but not miR-192 target. [score:3]
These results confirm that the CTNNBIP1 3’-UTR sequence is recognized by miR-215 and that CTNNBIP1 is an miR-215 target. [score:3]
qRT-PCR analysis demonstrated that miR-215 expression was knocked down by 55% in the kidney cortices of the antagomir-215 -treated mice compared with those in the control mice (Fig. 7B). [score:3]
β-catenin is a signaling molecule downstream of CTNNBIP1 that is involved in miR-215 -mediated MMC phenotypic transition and fibronectin expression. [score:3]
β-catenin is a signaling molecule downstream of CTNNBIP1 that is involved in miR-215 -mediated phenotypic transition and fibronectin expression. [score:3]
Moreover, qRT-PCR analysis demonstrated that CTNNBIP1 overexpression significantly decreased α-SMA and fibronectin levels in TGF-β1 and miR-215 mimic co -treated MMCs (Figs. 5G and H). [score:3]
Most importantly, we provided evidence, both in vitro and in vivo, that miR-215 is a central component of MC transdifferentiation pathways that contribute to DN pathology by targeting CTNNBIP1 and promoting Wnt/β-catenin signaling. [score:3]
0058622.g006 Figure 6. MMCs were transfected with CTNNBIP1 siRNA (30 nM) and/or an miR-215 inhibitors (100 nM) as indicated. [score:3]
When TGF-β1 -treated cells were transfected with the miR-215 inhibitor, the TGF-β1 -induced decrease in luciferase activity in CTNNBIP1 3’-UTR reporter -transfected cells was abolished. [score:3]
CTNNBIP1 is a potential miR-215/192 target. [score:3]
These results indicate that the effect of miR-215 on TGF-β1 -induced MMC phenotypic transition and fibronectin expression depends on CTNNBIP1. [score:3]
As shown in Figs. A and B, there was a significant increase in both miR-192 and miR-215 expression in MMCs that were treated with 30 mM glucose for 48 hours. [score:3]
These results indicated that miR-215, but not miR-192, recognizes the CTNNBIP1 gene 3’-UTR sequence and thereby decreases CTNNBIP1 expression. [score:3]
Moreover, miR-215 inhibitor pretreatment significantly decreased the TGF-β1 -mediated increase in activated β-catenin protein (Fig. 6A), α-SMA (Figs. 5B, C and E) and fibronectin (Figs. 5B and D) levels in MMCs. [score:3]
MMCs were transfected with CTNNBIP1 siRNA (30 nM) and/or an miR-215 inhibitors (100 nM) as indicated. [score:3]
Their study revealed that miR-215 mimic transfection of MMCs had no effect on α-SMA expression in the absence or presence of TGF-β1. [score:3]
Most importantly, these changes were largely abolished when TGF-β1 -treated MMCs were co -transfected with the miR-215 inhibitor in combination with CTNNBIP1 siRNA (Figs. 5B–E). [score:3]
0058622.g004 Figure 4Cultured MMCs were transfected with an miR-215 mimic (100 nM), an miR-215 inhibitor (100 nM) or an miR-control (100 nM), followed by treatment with TGF-β1 (10 ng/ml) for 48 hours. [score:3]
Interestingly, luciferase reporter assays further revealed that CTNNBIP1 is a direct miR-215 target in MMCs that are untreated or TGF-β1 -treated. [score:3]
Interestingly, we observed that CTNNBIP1 siRNA reversed the effects of an miR-215 inhibitor on the TGF-β1 -mediated MMC phenotypic transition, indicating that CTNNBIP1 is involved in miR-215 -mediated pro-differentiation effects in the TGF-β1 -induced MMC phenotype transition. [score:3]
Magnification, ×200 in E. Cultured MMCs were transfected with an miR-215 mimic (100 nM), an miR-215 inhibitor (100 nM) or an miR-control (100 nM), followed by treatment with TGF-β1 (10 ng/ml) for 48 hours. [score:3]
These results indicate that miR-215, but not miR-192, targets endogenous CTNNBIP1 in MMCs. [score:3]
a, untreated MMCs; b-d, MMCs treated with TGF-β1 alone, TGF-β1 plus miR-215 inhibitor, or TGF-β1 plus miR-215 mimic, respectively. [score:3]
Furthermore, when MMCs were co -transfected with the miR-215 mimic in combination with CTNNBIP1 siRNA, α-SMA and fibronectin expression were significantly increased relative to the control group. [score:3]
In conclusion, our results demonstrate that miR-215 is a key endogenous gene-silencing factor that mediates TGF-β1 -induced MC activation and fibronectin expression via a CTNNBIP1/β-catenin pathway. [score:3]
MMCs were transfected with CTNNBIP1 siRNA (30 nM) and/or an miR-215 inhibitor (100 nM) as indicated. [score:3]
MMCs were treated with an miR-215 mimic (100 nM), an miR-215 inhibitor (100 nM) or the miR-control (100 nM) for 24 hours, miR-215 levels were determined by qRT-PCR (B), and subsequently analyzed for the level of CTNNBIP1 protein byting (E). [score:3]
MMCs were transfected with CTNNBIP1 expression plasmids (0.25 µg plasmid/well) or miR-215 mimics (100 nM) as indicated. [score:3]
In this study, we addressed whether the miR-215/CTNNBIP1 pathway was involved in TGF-β1 -induced MMC phenotypic transition by regulating β-catenin activity. [score:2]
MiR-215 expression in MMCs after TGF-β1 stimulation displayed a similar trend (Figs. 1E and F). [score:2]
The development of miR-215 -based therapeutic strategies may attenuate or even reverse kidney fibrosis and dysfunction. [score:2]
Magnification, ×400 in H. In this study, we demonstrated for the first time that miR-215 plays a positive regulatory role in MC activation, which is associated with DN pathology. [score:2]
miR-215 regulates MMC phenotypic transition induced by TGF-β1. [score:2]
After establishing that miR-215 regulated α-SMA and fibronectin expression in MMCs via a CTNNBIP1/β-catenin -dependent pathway, we expanded our study to investigate whether these mechanisms were important in db/db mice. [score:2]
s were performed as described previously [29] using an miR-192 probe (5’-CTGACCTATGAATTGACAGCC-3’) and an miR-215 probe (5’-GTCTGTCAAATCATAGGTCAT-3’). [score:1]
To investigate the involvement of the miR-192/215 family in TGF-β1 -induced MC phenotypic transition, MMCs were transfected with an miR-192 or an miR-215 inhibitor. [score:1]
Furthermore, experiments using specific antagomir treatment in db/db mice provide evidence for the functional importance of miR-215 in diabetic nephropathy pathogenesis in vivo. [score:1]
Northern blots were performed as described previously [29] using an miR-192 probe (5’-CTGACCTATGAATTGACAGCC-3’) and an miR-215 probe (5’-GTCTGTCAAATCATAGGTCAT-3’). [score:1]
Cells were then co -transfected with a reporter construct (pMIR -null REPORT plasmid, pMIR-CTNNBIP1 3′-UTR, pMIR-CTNNBIP1 3′-UTR-Mut) and miR-215 mimic, miR-192 mimic or miR-control. [score:1]
CTNNBIP1 is involved in miR-215 -mediated MMC phenotypic transition. [score:1]
a, untreated MMCs; b–e, MMCs treated with miR-215 mimic, β-catenin siRNA alone, miR-215 mimic plus CTNNBIP1 siRNA, or miR-215 mimic plus CTNNBIP1 siRNA plus β-catenin siRNA, respectively. [score:1]
In contrast, a specific miR-215 mimic enhanced TGF-β1 -induced MMC changes (Fig. 4A and B). [score:1]
Therefore, we further examined the functional involvement of CTNNBIP1 in TGF-β1 -induced miR-215 -mediated MMC phenotypic transition. [score:1]
In the same study, we verified that miR-215 participates in TGF-β1 -mediated MMC phenotypic transition. [score:1]
These data provide evidence that transdifferentiation from MC to myofibroblast can be induced by TGF-β1 and miR-215 participates in the MC phenotypic transition. [score:1]
MMCs were transfected with an miR-215 mimics (100 nM) and/or CTNNBIP1 siRNA (30 nM) as indicated. [score:1]
[1 to 20 of 80 sentences]
3
[+] score: 38
Likewise, we observed downregulation of miR-215 in tumors of both types, and downregulation of miR-133a in CAC but not APC tumors. [score:7]
In contrast, Olaru et al. observed an upregulation of miR-215 in colitis -associated neoplasia [25]. [score:4]
Of note, our data also indicates that miR-215 is downregulated in APC and CAC tumors and in human colon tumors [18], [21]– [23], [37]. [score:4]
We focused on the 4 miRNAs that were differentially expressed in early stage lesions of both genetic and inflammatory origin (miR-215, miR-31, miR-708, miR-135b). [score:3]
The cause of this discrepancy is unclear, but is tempting to speculate the differential expression of miR-215 is reflected by the stage of transformation, dysplasia versus carcinoma. [score:3]
Eight high priority miRNAs were identified: miR-215, miR-137, miR-708, miR-31, and miR-135b were differentially expressed in APC tumors and miR-215, miR-133a, miR-467d, miR-218, miR-708, miR-31, and miR-135b in colitis -associated tumors. [score:3]
Nevertheless, there is evidence that miR-31 [12]– [17],, miR-135b [13]– [15], [20], [21], [33], and miR-215 [18], [21]– [23], [37] are differentially expressed in fully transformed colonic epithelial cells. [score:3]
Four of these (miR-215, miR-708, miR-31, and miR-135b) were common to both tumors types, and dysregulation of these miRNAs was confirmed in an independent sample set. [score:2]
Int J Cancer 30 Boni V Bitarte N Cristobal I Zarate R Rodriguez J 2010 miR-192/miR-215 Influence 5-Fluorouracil Resistance through Cell Cycle-Mediated Mechanisms Complementary to its Posttranscriptional Thymidilate Synthase Regulation. [score:2]
This curation step reduced the number of high probability differentially expressed miRNAs in APC tumors to 5 and the number of such miRNAs in CAC tumors to 7. As shown in Table 1, two miRNAs were repressed in APC tumors (miR-215 and miR-137), compared to adjacent control epithelium, whereas 3 miRNAs were induced (miR-708, miR-31, miR-135b). [score:2]
Three miRNAs were induced in both APC and CAC samples (miR-31, miR-135b, and miR-708) and 1 miRNA was repressed in both APC and CAC samples (miR-215). [score:1]
Nevertheless, we were able to validate our four most prominent miRNAs (miR-215, miR-708, miR-135b, miR-31) in an independent set of APC and CAC tumors. [score:1]
Summary of top GO functions identified for miR-215, miR-31, miR-135b, and miR-708 by Ingenuity Pathway Analysis. [score:1]
As shown in Figure 4, repression of miR-215 was confirmed in both CAC and APC tumor samples, whereas induction of miR-708, miR-31, and miR-135b was likewise confirmed in tumors of both origins. [score:1]
Mol Cancer Ther 31 Song B Wang Y Titmus MA Botchkina G Formentini A 2010 Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells. [score:1]
[1 to 20 of 15 sentences]
4
[+] score: 34
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-22, hsa-mir-29a, hsa-mir-30a, hsa-mir-29b-1, hsa-mir-29b-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-127, mmu-mir-132, mmu-mir-133a-1, mmu-mir-136, mmu-mir-144, mmu-mir-146a, mmu-mir-152, mmu-mir-155, mmu-mir-10b, mmu-mir-185, mmu-mir-190a, mmu-mir-193a, mmu-mir-203, mmu-mir-206, hsa-mir-148a, mmu-mir-143, hsa-mir-10b, hsa-mir-34a, hsa-mir-203a, hsa-mir-215, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-143, hsa-mir-144, hsa-mir-152, hsa-mir-127, hsa-mir-136, hsa-mir-146a, hsa-mir-185, hsa-mir-190a, hsa-mir-193a, hsa-mir-206, mmu-mir-148a, 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-22, mmu-mir-29a, mmu-mir-29c, mmu-mir-34a, mmu-mir-337, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-155, mmu-mir-29b-2, hsa-mir-29c, hsa-mir-34b, hsa-mir-34c, hsa-mir-378a, mmu-mir-378a, hsa-mir-337, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-411, mmu-mir-434, hsa-mir-486-1, hsa-mir-146b, hsa-mir-193b, mmu-mir-486a, mmu-mir-540, hsa-mir-92b, hsa-mir-411, hsa-mir-378d-2, mmu-mir-146b, mmu-mir-193b, mmu-mir-92b, mmu-mir-872, mmu-mir-1b, mmu-mir-3071, mmu-mir-486b, hsa-mir-378b, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, mmu-mir-378b, hsa-mir-203b, mmu-mir-3544, hsa-mir-378j, mmu-mir-133c, mmu-let-7j, mmu-mir-378c, mmu-mir-378d, mmu-let-7k, hsa-mir-486-2
Down-regulated miRNAs Up-regulated target genes mmu-mir-148a ARL6IP1, ARPP19, ATP2A2, CCNA2, CSF1, EGR2, ERLIN1, ERRFI1, FIGF, GADD45A, GMFB, ITGA5, KLF4, KLF6, LIMD2, MAFB, NFYA, PDIA3, PHIP, PPP1R10, PPP1R12A, PTPN14, RAI14, RSBN1L, SERPINE1, SIK1, SLC2A1, TMEM127, TMSB10, TMSB4X mmu-mir-411 APOLD1, SPRY4 mmu-mir-136 RYBP, ARL10, GLIPR2, UGGT1 Up-regulated miRNAs Down-regulated target genes mmu-mir-34a/c DAB2IP, DMWD, EVI5L, FAM107A, MAZ, SPEG, TFRC, TTC19 mmu-mir-92b COL1A2, DAB2IP, G3BP2, HOXC11, LBX1, NFIX, PKDCC, PRKAB2 mmu-mir-132 ACTR3B, AMD1, GPD2, HBEGF, KBTBD13, KCNJ12, PRRT2, SREBF1, TLN2 mmu-mir-146a IRAK1, TLN2 mmu-mir-152 EML2, GPCPD1, NFIX, RPH3AL, SH3KBP1, TFRC, TRAK1, UCP3 mmu-mir-155 DUSP7, G3BP2 mmu-mir-185 DAB2IP, FAM134C, SYNM, TMEM233 mmu-mir-203 APBB2, CACNG7, FKBP5, GDAP1, HBEGF, KCNC1, SIX5, TMEM182 mmu-mir-206 DMPK, G3BP2, GPD2, KCTD13, MKL1, SLC16A3, SPEG mmu-mir-215 KLHL23 Figure 5The network displays the predicted interactions between age-related miRNAs and mRNAs from the sequencing and was generated using Cytoscape (version 3.0, www. [score:17]
Down-regulated miRNAs Up-regulated target genes mmu-mir-148a ARL6IP1, ARPP19, ATP2A2, CCNA2, CSF1, EGR2, ERLIN1, ERRFI1, FIGF, GADD45A, GMFB, ITGA5, KLF4, KLF6, LIMD2, MAFB, NFYA, PDIA3, PHIP, PPP1R10, PPP1R12A, PTPN14, RAI14, RSBN1L, SERPINE1, SIK1, SLC2A1, TMEM127, TMSB10, TMSB4X mmu-mir-411 APOLD1, SPRY4 mmu-mir-136 RYBP, ARL10, GLIPR2, UGGT1 Up-regulated miRNAs Down-regulated target genes mmu-mir-34a/c DAB2IP, DMWD, EVI5L, FAM107A, MAZ, SPEG, TFRC, TTC19 mmu-mir-92b COL1A2, DAB2IP, G3BP2, HOXC11, LBX1, NFIX, PKDCC, PRKAB2 mmu-mir-132 ACTR3B, AMD1, GPD2, HBEGF, KBTBD13, KCNJ12, PRRT2, SREBF1, TLN2 mmu-mir-146a IRAK1, TLN2 mmu-mir-152 EML2, GPCPD1, NFIX, RPH3AL, SH3KBP1, TFRC, TRAK1, UCP3 mmu-mir-155 DUSP7, G3BP2 mmu-mir-185 DAB2IP, FAM134C, SYNM, TMEM233 mmu-mir-203 APBB2, CACNG7, FKBP5, GDAP1, HBEGF, KCNC1, SIX5, TMEM182 mmu-mir-206 DMPK, G3BP2, GPD2, KCTD13, MKL1, SLC16A3, SPEG mmu-mir-215 KLHL23 Figure 5The network displays the predicted interactions between age-related miRNAs and mRNAs from the sequencing and was generated using Cytoscape (version 3.0, www. [score:17]
[1 to 20 of 2 sentences]
5
[+] score: 29
In this study, there were 8 upregulated miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133a-1-5p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p) and 1 downregulated miRNA (mir-215-5p) present as potential targets for differentiation between gram -negative and gram -positive bacterial infection. [score:9]
Following exposure to gram -positive bacteria in the injection and skin graft mo dels, 7 upregulated miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p) and 1 downregulated miRNA (mir-215-5p) were found. [score:7]
In addition, following exposure to gram -positive bacteria in the cut mo del, only 2 miRNAs (mir-133a-1-3p, mir-133a-2-3p) were upregulated and 1 miRNA (mir-215-5p) was downregulated. [score:7]
Upon gram -positive bacterial infection, 9 miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133a-1-5p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p, mir-215-5p) showed upregulation greater than 4-fold with a p-value < 0.01. [score:4]
It was revealed that a total of 9 miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133a-1-5p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p, mir-215-5p) showed differences greater than 4-fold with p-value < 0.01 between the 2 libraries (Table  1). [score:1]
Small RNA deep sequencing and qPCR results of five selected miRNAs (mir-133a-1-3p, mir-127-3p, mir-25-3p, mir-191-5p, and mir-215-5p) were generally in agreement, with a Pearson correlation value of 0.921 (Additional file 2). [score:1]
[1 to 20 of 6 sentences]
6
[+] score: 26
The expression of miR-215-5p, miR-199a-5p & 3p was analyzed by real-time PCR and Northern blot (Fig. 7C–F), demonstrating that the induction of miR-215, miR-199a-5p&3p after UUO was inhibited in PT-p53- KO mice. [score:5]
Previous results demonstrated that p53 directly induced miR-215 expression 33, which is known to be involved in increased collagen production and the progression of diabetic nephropathy by regulating the CTNNBIP1/β-catenin pathway 20. miR-199a-5p (previously called miR-199a) and miR-199a-3p (previously called miR-199a*) are two mature forms derived from the same precursor in the human genome 34 35. [score:5]
The expressions of three miRNAs, miR-215-5p and miR-199a-5p&3p, were found to be consistently high in wide type mice with UUO, and they were decreased in renal cortex of global p53 knockout mice with UUO. [score:4]
However, the two down-regulated miRNAs, miR-215-5p and miR-199a-5p were correlated with the amelioration of renal fibrosis 20 21. [score:4]
The induction of miR-215, miR-199a-5p, and miR-199a-3p after UUO was suppressed in PT-p53- KO mice. [score:3]
The induction of miR-215, miR-199a-5p&3p after UUO was suppressed in PT-p53- KO mice. [score:3]
Total RNA (10 μg per lane) was analyzed by Northern blotting as described in the concise Methods section using a [32]p-labeled probe of miR-215, miR-199a-5p, and miR-199a-3p. [score:1]
Previous studies have demonstrated that both miR-215-5p and miR-199a-5p were related to the renal fibrosis 20 21, hence, we focused on the miR-199a-3p. [score:1]
[1 to 20 of 8 sentences]
7
[+] score: 16
Dot plots show the expression levels of miR-146a, miR-193b, miR-205, miR-215, miR-467a, miR-150, and miR-486 measured for MV, MV-free plasma, and brains from NI, NCM, and CM conditions, expressed as normalized values as compared to the expression of a panel of control miRNA in each case. [score:4]
The differential expression profiles of these selected miRNA (miR-146a, miR-150, miR-193b, miR-205, miR-215, miR-467a, and miR-486) were analyzed in mouse MV, MV-free plasma, and brain tissue by quantitative reverse transcription PCR (RT-qPCR). [score:3]
A further four miRNA—miR-150, miR-215, miR-467a, and miR-486 showed the same directional change in abundance as in the, without reaching significance (Fig.   4). [score:2]
NI MV OpenArray RT-qPCR hsa-miR-328 − 2.5* ± 0.93Not tested [a] hsa-miR-335* − 3.0* ± 1.13Not tested [a] mmu-miR-16* 2.8** ± 0.65Not tested [a] mmu-miR-21* 5.0** ± 0.88Not tested [a] mmu-miR-297a* 5.8* ± 1.60Not tested [a] mmu-miR-685 3.0* ± 1.00Not tested [a] mmu-miR-1949 5.0* ± 1.69Not tested [a] hsa-miR-590-5p Unique to NINot validated [b] rno-miR-450 Unique to CMNot validated [b] mmu-miR-10b 2.7* ± 0.85Not validated [b] hsa-miR-146a 3.2** ± 0.68 7.2* ± 2.74 hsa-miR-150 1.8* ± 0.64 2.7 (ns) ± 2.26 hsa-miR-205 2.3* ± 0.75 − 0.5 (ns) ± 1.89 hsa-miR-486 2.3*** ± 0.18 4.7 (ns) ± 1. 45 mmu-miR-193b − 2.7** ± 0.62 − 7.5* ± 0 62 mmu-miR-215 2.1* ± 0.554.6 (ns) ± 99.39 [c] mmu-miR-467a − 2.0* ± 0.69 − 5.6 (ns) ± 0.96 The list of significantly differentially expressed miRNA in CM vs NI MV from the was compared with the results obtained by. [score:2]
The results are presented as follows: significant changes in MV – miR-146a and miR-193b, significant changes in the brain—miR-205, miR-215, and miR-467a, no significant changes—miR-150 and miR-486. [score:1]
No significant change in the abundance of miR-150, miR-205, miR-215, miR-467a, and miR-486 in MV following Plasmodium infection. [score:1]
The database was searched with the full names of each murine miRNA as per the ThermoFisher Scientific product information and miRBase version 21: mmu-miR-16-1-3p, mmu-miR-21a-3p, mmu-miR-146a-5p, mmu-miR-150-5p, mmu-miR-193b-3p, mmu-miR-205-5p, mmu-miR-215-5p, mmu-miR-297a-3p, mmu-miR-328-3p, mmu-miR-335-3p, mmu-miR-467a-5p, mmu-miR-486a-5p, mmu-miR-685, mmu-miR-1949, and rno-miR-10b-5p. [score:1]
The results of these are denoted as * = 0.05–0.01, ** = 0.01–0.0001, *** ≤ 0.0001 No significant change in the abundance of miR-150, miR-205, miR-215, miR-467a, and miR-486 in MV following Plasmodium infectionOf the seven miRNA of interest tested by RT-qPCR, miR-146a and miR-193b showed the same significant change in abundance as in the OpenArray (from Fig.   2b). [score:1]
All the remaining miRNA (Table  1, miR-146a, miR-150, miR-193b, miR-205, miR-215, mir-467a, and miR-486) were tested on MV samples as per the and also on MV-free plasma and brain tissue from NI, NCM, and CM mice. [score:1]
[1 to 20 of 9 sentences]
8
[+] score: 15
Therefore, downregulation of miR-215 could promote EMT phenotype in downregulation of E-cadherin and promote EMT phenotype in the cycling hypoxia-selected subpopulation. [score:7]
miR215 suppresses EMT by suppressing the mesenchymal transcription factor ZEB2 and increasing the E-cadherin level [39]. [score:5]
In addition to miRNA200c and miR205, the cycling hypoxia-selected subpopulation showed decreased miR215 expression (Figure 6e). [score:3]
[1 to 20 of 3 sentences]
9
[+] score: 14
To validate the microarray results, the expressions of five miRNAs were quantified using real-time quantitative PCR, including two up-regulated (miR-23a-3p and miR-215-5p) and three down-regulated (miR-27b-3p, miR-101a-3p, and miR-6394) miRNAs (Fig.   2d). [score:9]
Only 15 miRNAs from the 64 DEMs had validated target genes in IPA by target filter analysis, including miR-6349, miR-101a-3p, miR-6394, miR-126a-3p, miR-721, miR-143-3p, miR-497a-5p, miR-93-5p, miR-215-5p, miR-199a-3p, miR-23a-3p, miR-27b-3p, miR-2861, miR-30a-5p, and miR-370-3p. [score:5]
[1 to 20 of 2 sentences]
10
[+] score: 14
As shown in Figure 6, qualitative qPCR validated that ssc-miR-146a-5p, ssc-miR-221-5p and ssc-miR-148b-3p were significantly upregulated by LPS, and ssc-miR-215 and ssc-miR-192 were downregulated. [score:7]
Similarly, five miRNAs (ssc-miR-192, 4_16129, 13_5595, ssc-miR-215 and ssc-miR-429) were significantly downregulated (Table 3). [score:4]
Differential expressions of five selected miRNAs (ssc-miR-146a-5p, ssc-miR-221-5p, ssc-miR-148b-3p, ssc-miR-215 and ssc-miR-192) were validated by quantitative polymerase chain reaction (qPCR). [score:3]
[1 to 20 of 3 sentences]
11
[+] score: 10
IsomiRs in other tissues such as isomiRs of miR-215 in the intestine (Additional file 11: Figure S3), miR-192-5p in the liver (Additional file 12: Figure S4) and miR-3473f-pre in the testis (Additional file 13: Figure S5 and Additional file 14: Figure S6) display similar isomiR expression. [score:3]
IsomiRs of miR-215 display more expanded or restricted expression with respect to tissues. [score:3]
Eli Lilly investigated the isomiR expression of pancreas tissue specific and enriched miRNAs and the analysis revealed that isomiRs generally mirror their parent miRNA expression (Additional file 10: Figure S2), but some isomiRs are more tissue specific than others as shown for miR-215 in the intestines (Additional file 11: Figure S3) and miR-217-5p in the pancreas (Additional file 10: Figure S2). [score:3]
IsomiRs of miR-215 in the intestine. [score:1]
[1 to 20 of 4 sentences]
12
[+] score: 9
The TaqMan® Array Human MicroRNA Card contained all 13 possible miRs predicted to target IRAK-1, and 24 h HG-stimulation caused the downregulation of seven endothelial miRs: miR-146a-5p, miR-339-5p, miR-874-3p, miR-125-3p, miR-431-5p, miR-192-5p, and miR-215-5p (Figure 2A). [score:6]
HG stimulation for 24 h revealed that seven miRs, miR-146a-5p, miR-339-5p, miR-874-3p, miR-125-3p, miR-431-5p, miR-192-5p, and miR-215-5p, were downregulated by HG, as compared with unstimulated control. [score:3]
[1 to 20 of 2 sentences]
13
[+] score: 9
Evidently, TA-p73/p63 appears to increase E-cadherin expression (a negative regulator of EMT), by suppressing ZEB1/2 through its target miRs, such as miR-192, miR-215, miR-145, miR-203, miR-200b, miR-200c, miR-183, miR-92a/b, miR-132, and miR-30a-e [45]. [score:8]
However, this does not explain how stress related miRNAs, such as miR-34, miR-192, and miR215, are produced in a p53 -dependent manner in response to DNA damage. [score:1]
[1 to 20 of 2 sentences]
14
[+] score: 9
Previously, it was reported that p53, another well-known tumor suppressor, upregulates the transcription of tumor-suppressor miRNAs such as miR-34a/b/c/, miR-107, miR-145, miR-192, and miR-215, which regulate cell proliferation, apoptosis, and angiogenesis [29]. [score:9]
[1 to 20 of 1 sentences]
15
[+] score: 7
Direct targets of p53 include the already mentioned miR-34 and also miR-192, miR-194 and miR215, which then modulate MDM2 expression [15]. [score:6]
One of the most elegant works provided evidence that miR-192, miR-194 and miR-215 can be transcriptionally activated by p53 [15]. [score:1]
[1 to 20 of 2 sentences]
16
[+] 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-17, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, mmu-let-7g, mmu-let-7i, mmu-mir-124-3, mmu-mir-9-2, mmu-mir-134, mmu-mir-137, mmu-mir-138-2, mmu-mir-145a, mmu-mir-24-1, hsa-mir-192, mmu-mir-194-1, mmu-mir-200b, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-215, hsa-mir-221, hsa-mir-200b, mmu-mir-296, mmu-let-7d, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-137, hsa-mir-138-2, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-134, hsa-mir-138-1, hsa-mir-194-1, mmu-mir-192, 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-24-2, mmu-mir-346, hsa-mir-200c, mmu-mir-17, mmu-mir-25, mmu-mir-200c, mmu-mir-221, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-138-1, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-106b, hsa-mir-200a, hsa-mir-296, hsa-mir-369, hsa-mir-346, gga-let-7i, gga-let-7a-3, gga-let-7b, gga-let-7c, gga-mir-221, gga-mir-17, gga-mir-138-1, gga-mir-124a, gga-mir-194, gga-mir-215, gga-mir-137, gga-mir-7-2, gga-mir-138-2, gga-let-7g, gga-let-7d, gga-let-7f, gga-let-7a-1, gga-mir-200a, gga-mir-200b, gga-mir-124b, gga-let-7a-2, gga-let-7j, gga-let-7k, gga-mir-7-3, gga-mir-7-1, gga-mir-24, gga-mir-7b, gga-mir-9-2, dre-mir-7b, dre-mir-7a-1, dre-mir-7a-2, dre-mir-192, dre-mir-221, dre-mir-430a-1, dre-mir-430b-1, dre-mir-430c-1, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-7a-3, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-17a-1, dre-mir-17a-2, dre-mir-24-4, dre-mir-24-2, dre-mir-24-3, dre-mir-24-1, dre-mir-25, dre-mir-92b, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-137-1, dre-mir-137-2, dre-mir-138-1, dre-mir-145, dre-mir-194a, dre-mir-194b, dre-mir-200a, dre-mir-200b, dre-mir-200c, dre-mir-430c-2, dre-mir-430c-3, dre-mir-430c-4, dre-mir-430c-5, dre-mir-430c-6, dre-mir-430c-7, dre-mir-430c-8, dre-mir-430c-9, dre-mir-430c-10, dre-mir-430c-11, dre-mir-430c-12, dre-mir-430c-13, dre-mir-430c-14, dre-mir-430c-15, dre-mir-430c-16, dre-mir-430c-17, dre-mir-430c-18, dre-mir-430a-2, dre-mir-430a-3, dre-mir-430a-4, dre-mir-430a-5, dre-mir-430a-6, dre-mir-430a-7, dre-mir-430a-8, dre-mir-430a-9, dre-mir-430a-10, dre-mir-430a-11, dre-mir-430a-12, dre-mir-430a-13, dre-mir-430a-14, dre-mir-430a-15, dre-mir-430a-16, dre-mir-430a-17, dre-mir-430a-18, dre-mir-430i-1, dre-mir-430i-2, dre-mir-430i-3, dre-mir-430b-2, dre-mir-430b-3, dre-mir-430b-4, dre-mir-430b-6, dre-mir-430b-7, dre-mir-430b-8, dre-mir-430b-9, dre-mir-430b-10, dre-mir-430b-11, dre-mir-430b-12, dre-mir-430b-13, dre-mir-430b-14, dre-mir-430b-15, dre-mir-430b-16, dre-mir-430b-17, dre-mir-430b-18, dre-mir-430b-5, dre-mir-430b-19, dre-mir-430b-20, mmu-mir-470, hsa-mir-485, hsa-mir-496, dre-let-7j, mmu-mir-485, mmu-mir-543, mmu-mir-369, hsa-mir-92b, gga-mir-9-1, hsa-mir-671, mmu-mir-671, mmu-mir-496a, mmu-mir-92b, hsa-mir-543, gga-mir-124a-2, mmu-mir-145b, mmu-let-7j, mmu-mir-496b, mmu-let-7k, gga-mir-124c, gga-mir-9-3, gga-mir-145, dre-mir-138-2, dre-mir-24b, gga-mir-9-4, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3, gga-mir-9b-1, gga-let-7l-1, gga-let-7l-2, gga-mir-9b-2
Mdm2 is negatively regulated by several miRNAs including miR-192 (Pichiorri et al., 2010), miR-194 (Pichiorri et al., 2010), miR-215 (Pichiorri et al., 2010), miR-221 (Kim et al., 2010), and miR-17 (Li and Yang, 2012) in different cellular contexts; however, whether these or other miRNAs regulate Mdm2 expression during the CNS development must be determined. [score:6]
[1 to 20 of 1 sentences]
17
[+] score: 6
It is a putative target of miR-215, which in turn is negatively regulated by androgens. [score:4]
Among these, insulin-like growth factor 1 gene (IGF1) was under positive regulation by androgens through miR-215 on GD 17.0, and through miR-30e, miR-1251, miR-709, miR-344f-3p, and miR-466l-5p on GD 18.0. [score:2]
[1 to 20 of 2 sentences]
18
[+] score: 5
Kim et al. [64] found that p53 up-regulated miR-200 and miR-192 family members and described the role of p53 in regulating epithelial-mesenchymal transition (EMT) in HCC through the induction of specific effector microRNAs including miR-141, miR-192, miR-194, miR-200b, miR-200c, and miR-215. [score:5]
[1 to 20 of 1 sentences]
19
[+] score: 4
MiR-342-5p, miR-3058-3p, let-7f-5p, miR-1961, miR-301b-3p, miR-98-5p, miR-1251-5p, miR-215-5p, miR-881-5p, miR-135a-2-3p, and miR-33-3p may regulate the expression of insulin-like growth factor 1 (IGF1) or insulin-like growth factor 2 (IGF2), two molecules that could rescue behavior and memory deficits via lowering A β levels [28, 29]. [score:4]
[1 to 20 of 1 sentences]
20
[+] score: 4
All miRNA mimics (miR-138, miR-18, miR-192, miR-215, miR-19, miR-204 and miR-211), miRNA inhibitors(miR-192 and miR-204) and small interfering RNA (siRNA) duplexes (siHOTTIP-1 and siHOTTIP-2) were products of Genepharma (Shanghai, China). [score:3]
20 nmol/L mimics of miR-138, miR-18, miR-192, miR-215, miR-19, miR-204, and miR-211, two HOTTIP siRNAs (siHOTTIP-1 and siHOTTIP-2)or NC RNA were transfected into SMMC7721,HepG2 and Hep3B HCC cells. [score:1]
[1 to 20 of 2 sentences]
21
[+] score: 4
Other miRNAs from this paper: mmu-mir-363
MiR-215 inhibited in vitro ovarian cancer cell proliferation, colony formation, migration and invasion, as well as in vivo tumor growth by targeting NOB1 [32]. [score:4]
[1 to 20 of 1 sentences]
22
[+] score: 4
However, miR-215 [31], miR-375 [32], miR-141, and miR-200c [33], miR-200a [34], miR-429 [35], miR-625 [36], and miR-18a [37] have already been shown to be inversely correlated with the EMT, and they were found downregulated in this subtype. [score:4]
[1 to 20 of 1 sentences]
23
[+] score: 3
MicroRNAs targeting MDM2: miR-192, miR-194, miR-215, miR-221, miR-605, miR-17-3p, miR-193a, miR-25, miR-32, miR-143, miR-145, miR-18b, miR-661 [reviewed in Ref. [score:3]
[1 to 20 of 1 sentences]
24
[+] score: 3
Another gene, Acads, which encodes an acyl-Coenzyme A dehydrogenase, is the putative target of mmu-miR-27a, mmu-miR-215, and mmu-let-7i. [score:3]
[1 to 20 of 1 sentences]
25
[+] score: 3
Among the known ~2,500 miRNA by deep sequencing of human genome [12], miR-192, miR-194, miR-204, miR-215 and miR-216 are highly expressed in kidney than other human tissues [13]. [score:3]
[1 to 20 of 1 sentences]
26
[+] score: 2
Braun et al. studied miR-192 and miR-215, which have the same "seed sequences", and showed they can both act as effectors as well as regulators of p53 [52]. [score:2]
[1 to 20 of 1 sentences]
27
[+] score: 1
These include mir-24-2, mir-30c-2, mir-125a, mir-130a, mir-196, mir-215, mir-218-2, and mir-367. [score:1]
[1 to 20 of 1 sentences]
28
[+] score: 1
These included miR-133a-3p, miR-133b-3p, miR-146b-3p, miR-200a-3p, miR-200b-3p, miR-215-5p, miR-223-3p, miR-1936 and miR-202-3p (Fig. 1A and Table 1). [score:1]
[1 to 20 of 1 sentences]
29
[+] score: 1
41 mmu-miR-33 −59.71 mmu-miR-222 1.23 mmu-miR-93 −1.52 mmu-miR-124 −97.01 mmu-miR-429 1.07 mmu-miR-192 −1.52 mmu-miR-129-5p −111.43 mmu-miR-100 −1.74 mmu-miR-210 −157.59 mmu-miR-20a −2 mmu-miR-134 −194.01 mmu-miR-137 −2 mmu-miR-215 −222.86 mmu-miR-194 −2.14 mmu-miR-452 −675.59 mmu-miR-196a −2.64 mmu-miR-223 −955.43 Differentiated sample versus control sample [DIF EBs d8/CONTROL EBs d8]. [score:1]
[1 to 20 of 1 sentences]