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42 publications mentioning hsa-mir-512-1

Open access articles that are associated with the species Homo sapiens and mention the gene name mir-512-1. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 441
Antagonizing DNA methylation using 5-aza-2'-deoxycytidine caused an efficient up-regulation of mature miR-296-5p and miR-512-5p in MDA-MB-231 cells that was enhanced when 5-aza-2'-deoxycytidine was combined with HDAC inhibitors: miR-296-5 pexpression was increased upon TSA treatment, a reported inhibitor of class I and II HDACs; in contrast, miR-512-5p was increased upon treatment with the pan-class I and II HDAC inhibitor Vorinostat (SAHA). [score:12]
Altogether our data suggest a mo del where epigenetic silencing of miR-296-5p and miR-512-5p expression in basal breast cancer cells releases hTERT expression from miRNA mediated suppression of gene expression. [score:9]
Altogether our data suggest that low miR-512-5p and miR-296-5p expression may have a role in assisting the establishment of a gene expression signature that includes hTERT upregulation, and contributes to the aggressiveness of basal type breast cancer. [score:8]
However, given the complexity of hTERT gene expression control and the numerous mRNAs targeted by miR-296-5p and miR-512-5p, we cannot completely exclude that indirect effects contribute to miR-296-5p and miR-512-5p dependent control of hTERT expression. [score:8]
Poor survival of basal type breast cancer with high hTERT expression appears to be recapitulated in specimen with enhanced expression of validated miR-296-5p or miR-512-5p target genes, including hTERT. [score:7]
Gene expression analyses suggest that high expression of hTERT and a panel of cancer relevant miR-296-5p and miR-512-5p target genes appear to be linked with reduced distant metastasis free survival and relapse free survival of basal breast cancer patients. [score:7]
We next used public gene expression datasets to test whether the expression of validated miR-296-5p or miR-512-5p target genes may have a special relevance in basal type breast cancer. [score:7]
HDAC inhibitors did not significantly alter miR-512-5p levels, suggesting that inhibiting HDAC activity is not sufficient to override silencing of miR-512-5p expression by DNA methylation (Figure 5D). [score:7]
This might provide first evidence that downregualtion of miR-296-5p, miR-512-5p in basal type breast cancer might help to promote the expression of a set of target genes, that could contribute to the aggressiveness of basal type breast cancer and hTERT expression in basal type breast cancer. [score:7]
Rescue experiments in breast cancer cells expressing hTERT lacking the 3’UTR revealed that this proliferation defects can be directly attributed to miR-296-5p and miR-512-5p dependent down-regulation of hTERT. [score:7]
miR-296-5p and miR-512-5p act as negative regulators of telomerase activity and telomere length by targeting hTERT expression. [score:6]
The observation of reduced distant metastasis free survival and relapse free survival of basal type breast cancer patients with increased miR-296-5p and miR-512-5p target gene expression signatures suggest that epigenetic regulation of miR-296 and miR-512 may be of relevance in this breast cancer subtype. [score:6]
Remarkably, TSA treatment does not affect miR-512-5p expression in this setup, indicating that the class I and II HDAC inhibitor SAHA has a specific relevance in regulating the epigenetic status of miR-512 genes. [score:6]
Low expression of miR-296-5p and miR-512-5p in breast cancer indicates that miR-296 and miR-512 hosting gene expression is tightly regulated. [score:6]
However, given the fact that multiple pathways impinge on telomerase expression, indirect effects triggered miR-296-5p or miR-512-5p on altered hTERT expression cannot be completely excluded. [score:6]
We consequently wished to test whether miR-296-5p and miR-512-5p are critical components that down-regulate hTERT expression in basal type breast cancer cells that are treated with epigenetic drugs. [score:6]
Disrupting miRNA gene silencing by the use of epigenetic drugs causes a dramatic miR-296-5p and miR-512-5p upregulation and concomitant reduction of hTERT expression that reduces the resistance to apoptotic stimuli. [score:6]
Recently, miR-512-5p has been shown to modulate the expression of the apoptosis regulator MCL-1, and miR-296-5p has been demonstrated to reduce cell proliferation of breast and prostate cancer cells by targeting SCRIB or HMGA1, respectively [35, 36, 42]. [score:6]
miR-296-5p and miR-512-5p target the 3’UTR of hTERT and are down-regulated in breast cancer. [score:6]
miR-512-5p and miR-296-5p regulate telomere homeostasis by targeting hTERT expression. [score:6]
Future efforts should aim to use a large set of specimen obtained from basal type breast cancer in order to experimentally validate the link between epigenetic silencing of miR-296 and miR-512, increased expression of validated miR-296-5p/miR-512-5p target genes and telomere homeostasis in a clinical setting. [score:5]
Mature miR-512-5p is encoded by the intergenic miR-512-1 and miR-512-2 genes located on human chromosome 19 and was reported to suppress apoptosis by targeting MCL-1 in gastric cancer and hTERT in head and neck squamous cell carcinoma [32, 43]. [score:5]
In line with this, stable expression of a miR-296-5p or miR-512-5p precursor stemloop construct in MDA-MB-231 basal type breast cancer cells, resulted in a significant reduction of hTERT expression and telomerase activity after approximately 18 population doublings. [score:5]
Real-time PCR analysis revealed that TSA or SAHA treatment does not significantly impact on the expression of HDACs, suggesting that observed alteration in miR-296-5p and miR-512-5p are not triggered via altered HDAC expression (Supplementary Figure 9A-9J). [score:5]
Increased hTERT and miR-296-5p/miR-512-5p target gene expression is linked to poor clinical outcome in basal type breast cancer. [score:5]
Ectopic hTERT expression rescues proliferation, DNA damage and apoptosis marker expression triggered by miR-296-5p or miR-512-5p. [score:5]
The 3’UTR of hTERT contains 3 predicted target sites for miR-296-5p and one target site for miR-512-5p (Figure 1D, 1J). [score:5]
However, distant metastasis free survival and relapse free survival appears to be significantly reduced in basal type breast cancer with increased miR-512-5p target gene expression (Figure 3I). [score:5]
Epigenetic silencing of miR-296 and miR-512 genes in basal type breast cancer cells releases hTERT from miRNA dependent suppression of gene expression. [score:5]
As expected, treatment with the DNMT inhibitor 5-aza-2'-deoxycytidine reduced DNA methylation levels of CpG rich regions of interest and mediated a 5 fold or 70 fold increase of miR-296-5p or miR-512-5p expression levels, respectively (Figure 5A, 5B). [score:5]
Figure 6 Epigenetic silencing of miR-296 and miR-512 genes in basal type breast cancer cells releases hTERT from miRNA dependent suppression of gene expression. [score:5]
Together, these data show that low expression of miR-296-5p and miR-512-5p ensures elevated hTERT expression to improve cell proliferation potential. [score:5]
We next set out to investigate whether hTERT expression and miR-296-5p or miR-512-5p target gene expression signatures impact on clinical parameters of defined subtypes of breast cancer. [score:5]
In analogy to this, we found that competing increased miR-512-5p expression in SAHA and 5-aza-2’-deoxycytidine treated MDA-MD-231 cells by transfecting antagomiR-512-5p, rescued hTERT expression (Figure 5I; top panel). [score:5]
Basal type breast cancer patients showing high expression of experimentally validated miR-512-5p target genes show poor survival. [score:5]
Introduction of antagomiR-296-5p or antagomiR-512-5p that target endogenous mature miR-296-5p or miR-512-5p, resulted in a significant increase of hTERT mRNA expression levels in both, MCF-7 and MDA-MB-231 cells (Figure 2B, 2D). [score:5]
Performing a series of gain and loss of function experiments we show that miR-296-5p and miR-512-5p have a relevant role in the direct regulation of hTERT expression in two different human breast cancer cell lines. [score:5]
Together, this indicates that miR-296-5p and miR-512-5p are regulators of telomerase expression that impact on telomerase activity and telomere homeostasis in breast cancer cells. [score:4]
This demonstrates that epigenetic regulation of miR-296-5p and miR-512-5p impacts on hTERT expression levels in basal type breast cancer cells. [score:4]
Together, these data may provide indications that miR-296-5p and miR-512-5p dependent regulation of hTERT is part of a miR-296-5p/miR-512-5p target gene signature that contributes to poor clinical outcome in basal type breast cancer. [score:4]
This suggests that direct targeting of the hTERT 3’UTR by miR-512-5p or miR-296-5p has a major contribution to the observed proliferation defects. [score:4]
Out of this panel, miR-296-5p and miR-512-5p are significantly down-regulated in human breast cancer specimen. [score:4]
This data is supported by down-regulation of miR-296-5p and miR-512-5p in basal type human breast cancer (Figure 1C). [score:4]
Together, this gives strong evidence that in breast cancer cells hTERT expression levels is directly controlled by miR-296-5p and miR-512-5p dosage. [score:4]
In accordance with hTERT mRNA expression data we found that ectopic introduction of miR-296-5p or miR-512-5p resulted in a significant reduction of overall telomerase activity in MCF-7 cells; this result was recapitulated by siRNA mediated knock down of hTERT (Figure 2E-2F). [score:4]
This suggests that miR-512-5p and miR-296-5p act as potent tumor suppressive miRNAs that exert their anti-proliferative function along multiple pathways that include the regulation of hTERT, the catalytic subunit of the telomerase complex. [score:4]
Additional validation experiments revealed that out of a panel of predicted and reported miR-512-5p target genes only COPZ1, MN1 and LZTR1 are down regulated after ectopic introduction of mimic-miR-512-5p in MDA-MB-231 cells (Supplementary Figure 7A-7H). [score:4]
These data support evidence for a link between miR-296-5p and miR-512-5p and the regulation of hTERT expression. [score:4]
DNA methylation analysis focused on CpG islands located in vicinity to the miRNA hosting genes, but also on CpG islands with a reported role in regulating miR-296-5p and miR-512-5p expression [37][42]. [score:4]
Together, this demonstrates that miR-296-5p and miR-512-5p have a central role in executing epigenetic regulatory circuits that control hTERT expression and telomere length in cancer cells. [score:4]
Ectopic introduction of mimic-miR-296-5p or mimic-miR-512-5p in MCF-7 luminal type or MDA-MB-231 basal type breast cancer cells caused an approximately 70% or 30% reduction of endogenous hTERT mRNA expression levels, respectively (Figure 2A, 2C). [score:3]
Low miR-296-5p and miR-512-5p expression levels in basal type breast cancer cell lines suggest that the respective miR-296, miR-512-1 and miR-512-2 genes might be subjected to efficient repression or gene silencing. [score:3]
J, K. : 3 independent experiments were carried out, error bars indicate statistical significance; to better visualize differences in miR-296-5p and miR-512-5p, respective expression levels were set “1” in MDA-MB-468 cells. [score:3]
miR-512-5p/RNU46 ΔCt values of Taq-man PCR miRNA expression analysis indicate that miR-512-5p levels are close to the detection limit in luminal and basal type breast cancer cells but also in human mammary epithelial cells (Figure 3K, Supplementary Figure 7M). [score:3]
Importantly, we found that ectopic expression of hTERT rescues miR-296-5p or miR-512-5p induced cell proliferation defects (Figure 4D and 4E). [score:3]
To validate the specificity of miR-296-5p and miR-512-5p for the 3’UTR of hTERT we generated hTERT 3’UTR luciferase reporter constructs that contain deletions of the individual miR-296-5p or miR-512-5p target sites (Figure 1D, 1J). [score:3]
Thus, low miR-512-5p expression is a general feature of primary breast epithelial but also breast cancer cells. [score:3]
We next validated that impaired proliferation of miR-296-5p or miR-512-5p transfected MDA-MB-231 basal type breast cancer cells is due to reduced hTERT expression. [score:3]
Functional validation revealed that miR-296-5p and miR-512-5p target specific sites in the 3’UTR of hTERT. [score:3]
This is consistent with the requirement of telomerase expression in cancer cells and anticipates clinical relevance for miR-296-5p and miR-512-5p. [score:3]
miR-296-5p and miR-512-5p suppress hTERT -mediated protection from apoptosis and senescence in basal type breast cancer cells. [score:3]
Consistent with an overall decrease in telomere length we found that the frequency of short telomeres increases whereas the frequency of long telomeres decreases in miR-296-5p or miR-512-5p overexpressing MDA-MB-231 cells (Supplementary Figure 4D). [score:3]
In line with this, targeting of endogenous miR-296-5p or miR-512-5p using antagomiRs increased cell proliferation rates (Figure 4A). [score:3]
We found that among candidate miRNAs that mediate at least 50% reduction of hTERT 3’UTR reporter activity, only miR-296-5p, miR-512-5p and miR-1207-5p showed significant down-regulation in breast cancer when compared to healthy tissue (Figure 1A, 1C, Supplementary Figure 2A). [score:3]
This suggests that miR-296-5p and miR-512-5p execute epigenetic programs that control hTERT expression in breast cancer cells. [score:3]
This prompted us to test whether epigenetic silencing of the miR-296-5p or miR-512-1 and miR-512-2 gene loci is aimed to ensure high hTERT expression. [score:3]
Importantly, due to dramatic differences of hTERT 3’UTR size and sequence content across vertebrate, targeting of hTERT by miR-296-5p and miR-512-5p is limited to human, chimpanzee and rhesus monkey. [score:3]
In contrast, miR-512-5p - hTERT target site interaction is limited to humans and chimpanzee (Supplementary Figure 2B). [score:3]
Performing a high-throughput luciferase reporter screen we show that miR-296-5p and miR-512-5p efficiently target the 3’UTR of hTERT. [score:3]
In particular, our data suggest that DNA methylation and histone de-acetylation collaborate as redundant epigenetic mechanisms to silence the expression of miR-296-5p and miR-512-5p in basal type breast cancer cells. [score:3]
Along these lines, the exploration of epigenetic inhibitors in more complex preclinical mo dels could provide valuable insights into the relevance of miR-296 and miR-512 in imposing an anti-tumor effect that includes telomere related pathways in basal type breast cancer. [score:3]
Epigenetic silencing of miR-296-5p and miR-512-5p ensures hTERT expression in basal-type breast cancer cells. [score:3]
The interplay between epigenetic gene silencing and miR-296/miR-512 to favor hTERT expression identifies basal type breast cancer as potential breast cancer subtype to explore telomerase related therapeutic approaches. [score:3]
miR-512-5p was reported to activate apoptotic pathways in lung and gastric cancer and target hTERT in head and neck squamous cell carcinoma [32, 41– 43]. [score:3]
Numbers indicate distance from miR-512-1. Bottom left panel, miR-512-5p expression in MDA-MB-231 cells treated with increasing concentrations of 5’-Aza-2’-deoxycytidine. [score:3]
Together, these data demonstrate target specificity of miR-296-5p and miR-512-5p for the 3’UTR of hTERT. [score:3]
Performing gain and loss of function experiments we found that hTERT expression and telomerase activity is under control of both, miR-296-5p and miR-512-5p. [score:3]
Remarkably, the extremely short hTERT 3’UTR in rodents does not contain miR-296-5p and miR-512-5p target sites (data not shown). [score:3]
We found that Hela cells transiently transfected with hTERT 3’UTR luciferase reporters carrying mutations in individual target sites for miR-296-5p or miR-512-5p show increased luciferase reporter activity when compared to cells transfected with a wild type 3’UTR luciferase reporter (Supplementary Figure 2C, 2D). [score:3]
Cells were transfected at day 0 and day 3 of the experiment; cumulative cell numbers were determined at day 6. (E) Ectopic hTERT expression from a retroviral vector rescues proliferation defects of miR-512-5p transfected MDA-MB-231 cells. [score:3]
This suggests that TSA/SAHA treatment increases miR-296-5p and miR-512-5p levels, resulting in reduced hTERT expression. [score:3]
Recent studies reported a role of miR-133a, miR-138, miR-541, miR-491-5p, miR-512-5p, miR-1182, miR-1207-5p and miR-1266 in the control of hTERT expression in various types of cancer cells [27– 33]. [score:3]
This highlights that DNA methylation and histone de-acetylation collaborate to silence miR-296-5p and miR-512-5p in basal type breast cancer cells to ensure increased hTERT expression, thus resulting in improved protection from apoptosis. [score:3]
Amongst miRNAs with reported targeting specificity for hTERT, miR-541, miR-512-5p and miR-1207-5p were able to efficiently reduce hTERT-3’UTR reporter activity in our screen; miR-133a was not represented in our candidate miRNAs list (Supplementary Figure 1B). [score:3]
In line with this, we observed telomere shortening in cells overexpressing mature miR-296-5p or miR-512-5p. [score:3]
We treated MDA-MB-231 cells with DNA methyltransferase and histone deacetylase inhibitors and measured mature miR-512-5p and miR-296-5p expression levels by classic Taq-man PCR. [score:3]
miR-512-5p was shown to target hTERT in head and neck squamous cell carcinoma [32]. [score:3]
We next wished to demonstrate that miR-296-5p and miR-512-5p impact on hTERT expression in classic breast cancer mo del cell lines. [score:3]
Figure 2 (A, C) Transient transfection of MCF-7 (A) or MDA-MB-231 (C) cells with hTERT specific siRNAs or miR-296-5p or miR-512-5p mimics causes a reduction of hTERT mRNA expression as determined by quantitative RT-PCR. [score:3]
A similar trend for miR-296-5p and miR-512-5p target genes was found in the GOBO dataset (Supplementary Figure 6F-6H; Supplementary Figure 7I-7K)[45]. [score:3]
We therefore focused our further study on the functional relevance of miR-296-5p and miR-512-5p in controlling hTERT expression in human breast cancer. [score:3]
Altogether, our data suggest that silencing of miR-296-5p and miR-512-5p in basal type breast cancer helps to establish high hTERT expression levels, and may contribute to basal type breast cancer aggressiveness and reduced patient survival. [score:3]
A series of luciferase reporter experiments were carried out in HeLa and MDA-MB-231 basal type breast cancer cells that display comparable expression levels of endogenous miR-296-5p or miR-512-5p, respectively (Supplementary Figure 3A-3B). [score:3]
In line with this, ectopic hTERT reduced p21 expression in miR-296-5p transfected cells and reduced γH2AX levels as well as PARP and Caspase 3 cleavage in miR-296-5p or miR-512-5p transfected cells (Figure 4F). [score:3]
Introducing deletions that disrupt the miR-512-5p target site in the 3’UTR of hTERT caused increased luciferase reporter activity in mimic-miR-512-5p transfected Hela and MDA-MB-231 cells when compared to the wild-type reporter constructs (Figure 1J-1L, Supplementary Figure 3G-3H). [score:2]
DNA methylation at Alu-repeats in vicinity to miR-512 genes suggested the involvement of epigenetic regulatory mechanisms [43]. [score:2]
miR-296 CpG-1 island (1751bp upstream of miR-296): Fw: 5’-GTGAAAGTAAGTTTTATTGATGGT-3’; Rv_ 5’-CAAAAAATTCCAAAAACCCTTAAA-3’, [37]; miR-296 CpG-2 island (88bp downstream of miR-296) : Fw: 5’-GTGTTAGGAGTGGAGATAGGATAGT-3’; Rv: 5’-TCAATAAAAATAAAAAAAACCTCC-3’; miR-512- CpG-1 island (2806bp upstream of miR-512-1): Fw: 5’-TTGTAATTTTAGTATTTTGGGAGGT-3’; Rv: 5’-AAAACAATCTCACTCTATTACCCAAAC-3’; miR-512 CpG-2 island, regulating the C19MC cluster (17692 bp upstream of miR-512-1) Fw_5’-TTTTTTTTGAGGGATTAGAATTTGTT-3’ RV_5’-CCCTAAACTTCCTAATTAAATAAAAAACTA-3’ PCR products were gel purified and cloned into pCR2.1 using the TA cloning kit (Invitrogen). [score:2]
Using a basal type breast cancer cell line, we show that increasing intracellular levels of mature miR-296-5p and miR-512-5p resulted in telomere shortening as well as induction of senescence and apoptosis, finally causing reduced cell proliferation. [score:1]
Of notice, ectopic introduction of miR-296-5p in MDA-MB-231 cells did not alter miR-512-5p levels; altered miR-512-5p levels did not change miR-296-5p levels. [score:1]
A prominent role of miR-512-5p in activating apoptosis programs in MDA-MD-231 cells was validated by of Annexin V staining (Supplementary Figure 8B). [score:1]
Analogous data were obtained using p53 proficient MCF-7 luminal breast cancer cells: introducing miR-296-5p mimics into luminal MCF-7 cells activated senescence and apoptosis pathways; ectopic miR-512-5p exclusively activated apoptosis (Supplementary Figure 8C, 8D). [score:1]
miR-512-5p and miR-296-5p have a reported role in various aspects of human cancer. [score:1]
In contrast, ectopic miR-512-5p causes a significant increase in subG1, indicative for the activation of apoptosis (Figure 4B). [score:1]
Ectopic miR-296-5p and miR-512-5p reduce telomerase activity, impair telomere maintenance and promote senescence and apoptosis in basal breast cancer cells. [score:1]
In line with this, miR-296-5p and miR-512-5p have an anti-proliferative function in MCF-7 cells (Supplementary Figure 8E). [score:1]
miR-296-5p and miR-512-5p contribute to poor survival. [score:1]
Figure 4 (A) Cumulative cell numbers of MDA-MB-231 cells transiently transfected with miRNA control, miR-296-5p or miR-512-5p mimics. [score:1]
We further show that miR-296 and miR-512 gene loci are subjected to gene silencing in basal type breast cancer cells. [score:1]
In contrast, ectopic miR-512-5p did not increase number of beta-galactosidase positive cells, thus selectively promoting apoptosis (Supplementary Figure 8A). [score:1]
miR-512-5p levels were quantified against RNU49. [score:1]
Epigenetic silencing of miR-296-5p and miR-512-5p protects MDA-MB-231 cells from apoptosis. [score:1]
We found that ectopic introduction of synthetic miR-296-5p or miR-512-5p causes a significant reduction of MDA-MB-231 cell proliferation (Figure 4A). [score:1]
In order to test the impact of miR-296-5p and miR-512-5p on cell proliferation we determined cumulative cell numbers of MDA-MB-231 basal type breast cancer cells with altered miR-296-5p and miR-512-5p levels. [score:1]
To test whether miR-296-5p or miR-512-5p dependent reduction of hTERT mRNA levels is paralleled by a reduction of telomerase activity we performed TRAP analysis. [score:1]
ΔCt values (Ct miR-512-5p – Ct RNU49) are indicated. [score:1]
miR-296-5p and miR-512-5p cause hTERT dependent cell proliferation defects in MDA-MB-231 basal type breast cancer cells. [score:1]
Top panel, Position of CpG islands analyzed for the miR-512-1 and miR-512-2 genes. [score:1]
This suggests that different HDACs collaborate with DNMTs to ensure efficient epigenetic silencing of miR-296 or miR-512. [score:1]
Similar to miR-512-5p, we show that a 5-fold increase of miR-296-5p in 5-aza-2'-deoxycytidine treated MDA-MD-231 cells increased to 32-fold or 42 fold when 5-aza-2'-deoxycytidine was used in combination with TSA or SAHA, respectively (Figure 5F). [score:1]
In line with gain of function experiments, competing endogenous miR-296-5p or miR-512-5p by transfecting MDA-MB-231 cells with antagomiR siRNAs increased hTERT 3’UTR luciferase activity (Supplementary Figure 3I). [score:1]
Together, this indicates that repression of miR-296-5p and miR-512-5p in basal type breast cancer cells releases hTERT from miRNA dependent repression, to enhance resistance to apoptosis and telomere maintenance, thus promoting cancer cell aggressiveness. [score:1]
This result was confirmed by western blotting showing that ectopic introduction of synthetic miR-512-5p results in increased levels of the DNA damage marker γH2AX and increased PARP and Caspase 3 cleavage (Figure 4C). [score:1]
miR-296-5p and miR-512-5p reduce cell proliferation. [score:1]
A mo del for miR-296-5p and miR-512-5p function in basal-type breast cancer. [score:1]
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[+] score: 162
In our study, the ectopic expression of miR-512-5p inhibited the HNSCC cell growth by down-regulation telomerase activity, telomere length and telomere -binding proteins, and the delivery of miR-512-5p into transplanted tumors in nude mice significantly reduced tumor growth. [score:8]
Overexpression of MiR-512-5p significantly suppress HNSCC cell proliferation by targeting hTERT in vivo and in vitro, our current results strongly suggest that miR-512-5p might serve as a potentially therapeutic agent for miRNA -based HNSCC therapy. [score:7]
In addition, overexpression of miR-512-5p in HNSCC cells could suppress cell proliferation and increase apoptosis in vitro and suppress tumor growth in vivo. [score:7]
To validate whether miR-512-5p directly repress identified mRNA targets through 3’UTR interactions, we cloned a sequence with the predicted target sites of hTERT or a mutated sequence to downstream of the pMIR luciferase reporter gene. [score:6]
We predicted potential direct targets of miR-512-5p by Targetscan Release 6.2., PicTar5 and miRanda 3.0 programs (S1 Table). [score:6]
The results showed that up-regulation of miR-512-5P led to remarkable inhibition of cell proliferation and significantly increased apoptosis in HNSCC cells. [score:6]
These results demonstrated that miR-512-5p suppresses tumor growth and hTERT protein expression in vivo. [score:5]
The prediction of potential targets revealed hTERT as a candidate target of miR-512-5p, which attracted our attention. [score:5]
Furthermore, the expression of hTERT protein was dramatically down-regulated in the miR-512-5p treatment group compared with the scramble group (Fig 4C). [score:5]
The list of the predicted target genes of miR-512-5P from the Targetscan (Release 6.2), PicTar5 and miRanda 3.0 programs. [score:5]
The results indicated that overexpression of miR-512-5p resulted in a significant decrease in luciferase expression in hTERT-3’UTR transfected cells, compared with the scramble. [score:4]
Obviously, the result showed that miR-512-5p mimic led to down-regulation of hTERT and TRF2 in CNE cells (Fig 3C). [score:4]
These data demonstrated that miR-512-5p regulated hTERT expression at the post-transcriptional level and influenced the telomere -binding proteins. [score:4]
0135265.g002 Fig 2(A) MTT assay showed that overexpression of miR-512-5p in CNE cells resulted in inhibition of cell growth in vitro. [score:4]
Validation of hTERT mRNA as a direct target of miR-512-5p in CNE cells. [score:4]
We next sought to explore whether miR-512-5P was capable of regulating telomerase activity in HNSCC cells, CNE cells were infected with miR-512-5P mimic and miR-512-5P-scramble, one day post-transfection, a remarkable inhibition of telomerase activity was observed in cells transfected with miR-512-5P mimic in comparison with the cells transfected with scramble, respectively (Fig 2C). [score:4]
Consistent with the microRNA array results, QRT-PCR further validates that miR-512-5p levels were down-regulated in telomerase positive cell lines (Fig 1B). [score:4]
MiR-512-5p suppresses tumor growth and hTERT expression in vivo. [score:4]
Our findings demonstrate that miR-512-5p has properties consistent with tumor suppressor function in HNSCC. [score:3]
It is thus of importance to recognize miR-512-5p as a potential useful tumor suppressor gene. [score:3]
MiR-512-5p is down-regulated in in telomerase positive HNSCC cell lines. [score:3]
In conclusion, we here report expression patterns of altered miRs in HNSCC and the potential role of miR-512-5p in telomerase -positive HNSCC cells. [score:3]
MiR-512-5P is markedly down-regulated in telomerase positive HNSCC cell lines. [score:3]
These results indicated that miR-512-5p could suppress telomerase activity in telomerase positive HNSCC cells. [score:3]
Among the miRs with significantly changed expression levels, miR-512-5P was the most dramatically decreased by 0.13-fold (p<0.01). [score:3]
Next Luciferase reporter assay was performed to demonstrate hTERT as a direct target of miR-512-5p in HNSCC cells. [score:3]
0135265.g001 Fig 1 (A) indicated that miR-512-5P was the most dramatically decreased among the miRs with significantly changed expression levels in telometase positive cell lines. [score:3]
Meanwhile, previous study reported activation of miR-512-5p by epigenetic treatment induces suppression of Mcl-1, resulting in apoptosis of gastric cancer cells [24]. [score:3]
The hTERT mRNA is a target of miR-512-5p. [score:3]
We next explored the possible targets of miR-512-5p in HNSCC cells through different computational programs. [score:3]
These research data suggest that the delivery of miR-512-5p could represent a novel therapeutic strategy in HNSCC therapy by targeting hTERT. [score:3]
The transduction of miR-512-5P mimic showed a significant inhibition of cell proliferation in CNE cells, in comparison with those transduced with scramble as determined by MTT assay (Fig 2A). [score:2]
The prediction of potential targets of miR-512-5p and luciferase reporter assay. [score:2]
The results of this study indicated telomerase -positive cells revealed significantly lower levels of miR-512-5p expression compared with telomerase -negative cells. [score:2]
MiR-512-5P suppresses HNSCC cell viability and induces apoptosis in vitro. [score:2]
The above plasmids and miR-512-5p mimic or miR-512-5p-scramble were transiently transfected into 293T cells and a dual luciferase reporter assay system was used to detect luciferase expression 48 h after tranfection. [score:2]
These results strongly suggested that miR-512-5p function in telomere maintenance involved telomerase and telomere length regulating. [score:2]
0135265.g003 Fig 3(A) Sequence of potential binding site of miR-512-5p in the 3’UTR of hTERT mRNA, mutations were introduced into the binding site for generation of mutated hTERT-3’UTR. [score:2]
MiR-512-5p suppresses telomerase activity and shortens telomere length in HNSCC cells. [score:2]
Real-time PCR analysis for miR-512-5p was performed using the TaqMan miR Kit (Applied Biosystems, USA). [score:1]
Cell culture and transfection of miR-512-5P mimic. [score:1]
However, transfection of miR-512-5p in mut-hTERT-3’UTR transfected cells did not display significant reduction of luciferase levels (Fig 3B). [score:1]
We then address the potential effects of miR-512-5p on telomere length in telomerase positive HNSCC cells. [score:1]
The nude mice were then randomized and divided into two groups, CNE-scramble group and CNE-miR-512-5p mimic group, respectively. [score:1]
We further investigated the effect of miR-512-5p on the expression of hTERT and TRF2 by Western blot. [score:1]
CNE cells treated with scramble or miR-512-5p mimic (150 nM for 24 h) were injected into the nude mice. [score:1]
These findings suggested that miR-512-5p was reduced in telomerase positive HNSCC cell lines. [score:1]
The hTERT gene was predicted to have at least one potential binding site at their 3’-UTRs for miR-512-5p (Fig 3A). [score:1]
The effect of miR-512-5p on CNE cell growth, apoptosis and telomere maintenance. [score:1]
About 1×10 [4] 293T cells were seeded into each well of 24-well plate and co -transfected with wide type or mutant reporter constructs together with miR-scramble or miR-512-5p using the lipofectamine 2000 (Invitrogen, USA). [score:1]
MiR-512-5p mimic and miR scramble were synthesized and purified by Guangzhou Ribobio. [score:1]
Furthermore, we observed that apoptosis rate weas significantly increased in miR-512-5P mimics -treated cells (Fig 2B). [score:1]
Data of tumor volume (Fig 4A) showed that CNE cells treated with scramble led to larger tumors more rapidly than miR-512-5p -transfected cells in nude mice(P<0.01). [score:1]
In vivo effect of miR-512-5p on CNE cell growth in nude mice. [score:1]
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3
[+] score: 31
MSC expression of the eight C19MC miRNAs could be grouped in three expression patterns: group A, which included miR-512-3p and -520c-3p, showed very low or undetectable expression in the MSCs; expression of the group B miR-520d-5p, 519b-3p and -524-5p was detected in at least one or both MSC cell lines, whereas miR-520f-3p, -517a-3p and -520g-3p in group C were all expressed all three MSC cell lines (Fig.   1b and Table  2). [score:11]
The numerical in brackets shows the ranking of each pathway Table 3 Common validated target genes shared between the C19MC-AAGUGC-miRNAs and the miR-302/-372 families AAGUGC-miRNASeed position [a] Target transcript miR-302/-372 C19MC miR-302c miR-520e I NIK[10, 15] miR-373 miR-520c I MT1-MMP, mTOR, SIRT1[14, 21] miR-372, -373 miR-520c, -520e I RelA[12] miR-302b, -372, -373 miR-520c, -520e I TGFβR2[9, 12] miR-520b, -520e I CD46[16] miR-302c miR-520c I MICA, MICB, ULBP2[17] miR-519a I RBL2[13] miR-512 IIa miR-519d, -520g IIb SMAD7[19, 20] miR-520g, -520h IIb DAPK2[18, 22] miR-302d, -372 miR-520b, -519b-3p, -520a-3p I CDKN1A[5, 6] miR-519e IIa miR-519d, -520h IIb [a]Group I seed position is the canonical nts 2-7; IIa is nts 1-6 and IIb is other non-canonical position, as defined in Fig.   2a The 2058 putative target genes were further subjected to GO analysis and KEGG pathway annotation (Fig.   3b-d). [score:7]
The numerical in brackets shows the ranking of each pathway Table 3 Common validated target genes shared between the C19MC-AAGUGC-miRNAs and the miR-302/-372 families AAGUGC-miRNASeed position [a] Target transcript miR-302/-372 C19MC miR-302c miR-520e I NIK[10, 15] miR-373 miR-520c I MT1-MMP, mTOR, SIRT1[14, 21] miR-372, -373 miR-520c, -520e I RelA[12] miR-302b, -372, -373 miR-520c, -520e I TGFβR2[9, 12] miR-520b, -520e I CD46[16] miR-302c miR-520c I MICA, MICB, ULBP2[17] miR-519a I RBL2[13] miR-512 IIa miR-519d, -520g IIb SMAD7[19, 20] miR-520g, -520h IIb DAPK2[18, 22] miR-302d, -372 miR-520b, -519b-3p, -520a-3p I CDKN1A[5, 6] miR-519e IIa miR-519d, -520h IIb [a]Group I seed position is the canonical nts 2-7; IIa is nts 1-6 and IIb is other non-canonical position, as defined in Fig.   2a The 2058 putative target genes were further subjected to GO analysis and KEGG pathway annotation (Fig.   3b-d). [score:7]
To obtain further supporting evidences on selective activation, expression of eight miRNAs spanning the C19MC cluster (Fig.   1a), but with different genomic structures, was selected for further experimentally verification; amongst the selected miRNAs, miR-512-3p is transcribed by the two miR-512-1 and-512-2 genes located at the 5’-end of the C19MC miRNA gene cluster; miR-520c-3p, -519b-3p and -520f-3p are single miRNA genes located between previously proposed exons; miR-524-5p and -517a-3p are two of three miRNA genes mapped on intron 18 and miR520d-5p and -520g-3p are two of four miRNAs mapped on intron 20 (Fig.   1a) [24]. [score:3]
Specific activation of the C19MC miR-512-5p by histone deacetylase inhibitors was also reported in human gastric cancer cells [43]. [score:3]
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[+] score: 30
Moreover, we describe for the first time an association of the up-regulation of micro -RNA species such as hsa-miR-512-3p/-515/-517/-518/-525 and down-regulation of hsa-miR-99a/-100/-145 with a cisplatin resistant phenotype in human germ cell tumors. [score:7]
According to our analysis, further micro -RNA species appeared either about 8-fold up-regulated (hsa-miR-512-3p/-515/-517/-518/-525) or about 10-fold down-regulated (hsa-miR-99a/-100/-145) in both NTERA-2-R/NTERA-2 and NCCIT-R/NCCIT cell line pairs. [score:7]
These were hsa-miR-512-3p/-515/-517/-518/-525 (up to 8.1-fold up-regulated) and hsa-miR-99a/-100/-145 (up to 10-fold down-regulated). [score:7]
Only hsa-miR-10b and has-miR-512-3p species were found to be up-regulated (2-8-fold) in all three cell lines. [score:4]
Only the has-miR-10b involved in breast cancer invasion and metastasis and has-miR-512-3p appeared to be up-regulated (2-3-fold) in all three cell lines. [score:4]
Moreover, new micro -RNA species such as hsa-miR-512-3p/-515/-517/-518/-525 or hsa-miR-99a/-100/-145, also potentially involved in cisplatin resistance, could be identified in the germ cell tumor cell lines studied here. [score:1]
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5
[+] score: 21
Sixteen of 359 miRNAs detected were differentially expressed between tumor and matched benign tissue (adjusted p < 0.05): 9 were upregulated (hsa-miR-19a; hsa-miR-512-3p; hsa-miR-27b; hsa-miR-20a; hsa-miR-28-3p; hsa-miR-200c; hsa-miR-151-3p; hsa-miR-223; hsa-miR-20b), and 7 downregulated (hsa-miR-22; hsa-miR-516-3p; hsa-miR-370; hsa-miR-139-5p; hsa-let-7e; hsa-miR-145-3p; hsa-miR-30c) in tumor tissue in comparison to matched benign tissue (Table 2). [score:9]
miRNA Expression Cancer association (Y/N) Upregulated (Y/N) hsa-miR-19a Common YY (10) hsa-miR-512-3p T and E only YN (11) hsa-miR-27b Common YY (12) and N (13) hsa-miR-20a Common YY (14) hsa-miR-28-3p Common YY (15) hsa-miR-200c Common YY (16) and N (17) hsa-miR-151-3p Common YY (18) hsa-miR-223 Common YY (19) and N (15) hsa-miR-20b Common YY (20) hsa-miR-22 T and E only YY (19, 21) and N (22) hsa-miR-516-3p T only N N/A hsa-miR-370 Common YY (23) hsa-miR-139-5p Common YN (24) hsa-let-7e Common YN (25) hsa-miR-145-3p T and E only YN (26) hsa-miR-30c Common YN (27) T, tumor; E, exosome. [score:6]
All nine upregulated tumor-tissue miRNAs were expressed in both tumor and plasma (both free and within exosomes), except for hsa-miR-512-3p, which was only present in tumor and within exosomes. [score:6]
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[+] score: 20
Irrespective of wild type or mutated or null p53, after radiation treatment, miR-302a and miR-302c up-regulated, and miR-518f down-regulated in colon cancer cells, whereas after SN38 treatment up-regulated miRNAs were miR-133a, miR-155, miR-204, miR-22, miR-512-3p, miR-517a, miR-517c and miR-708 in the all colon cancer cell lines. [score:10]
Irrespective of p53 status, after radiation miR-302a and miR-302c up-regulated, and miR-518f down-regulated in the all cell lines, whereas after SN38 treatment up-regulated miRNAs were miR-133a, miR-155-3p, miR-204, miR-22, miR-512-3p, miR-517a, miR-517c and miR-708 in the all cell lines (Figure 3, Table 1a). [score:10]
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7
[+] score: 18
The miR-512-3p and miR-522* were up-regulated between the normal cervical tissues and CINI and CINIII samples and had normal expression in cervical carcinoma. [score:6]
The expression pattern of miR-512-3p and its putative targets (Table S2) suggest that this miRNA may play an important role in the development of dysplasia in cervical tissues and is apparently less important during cell invasion. [score:6]
Two miRNAs exhibited relative increased expression in the transition from normal cervix to atypical dysplasia and decreased expression in the transition from atypical dysplasia to cervical carcinoma, namely miR-522* and miR-512-3p (Figure 4C). [score:5]
ERK/MAPK signaling (miR-203), PTEN signaling (miR-27a), VEGF signalling (miR-10a), p53 signaling (miR-205) and apoptosis signalling (miR-512-3p) were found once (Table 2 and table S3). [score:1]
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8
[+] score: 13
The miR-512/519a cluster was highly represented containing 14 upregulated miRNA while 2 members of the miR-17/92 cluster and its paralogs miR-106a/363 and miR-106b/25 showed down-regulation in hypoxic hESCs. [score:7]
Couple to this a number of publications have characterised the range of miRNAs expressed by hESC under standard culture conditions and in agreement with those we noted that three of the top ten upregulated miRNAs in hESCs (miR-4271,-4306, and miR-148b-3p), and members of the miR-512/519a and miR-302b/367 cluster are highly expressed in undifferentiated hESCs [32, 33]. [score:6]
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9
[+] score: 11
The expression levels of miR-1225-5p, miR-1909-5p, miR-512-5p, miR-3927, miR-1203, miR-2110, miR-501-5p, miR-648, miR-4729, miR-4475, miR-1914-3p and miR-5002-5p were downregulated in the children with CPHD. [score:6]
However, the expression levels of miR-1225-5p, miR-1909-5p, miR-512-5p, miR-3927, miR-1203, miR-2110, miR-501-5p, miR-648, miR-4729, miR-4475, miR-1914-3p and miR-5002-5p were downregulated (Fig. 2B) (P<0.05) in the children with CPHD compared with the normal controls. [score:5]
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10
[+] score: 11
The eight miRNAs selected included the most upregulated miRNAs (miR-512-3p, miR-377-5p, miR-433-3p and miR-1323) and most downregulated miRNAs (miR-33a-5p, miR-551b-3p, miR-3613-5p and miR-144-3p) in OS. [score:7]
Among these, miR-512-3p, miR-377-5p, miR-433-3p and miR-1323 were the greatest upregulated miRNAs, whereas miR-33a-5p, miR-551b-3p, miR-3613-5p and miR-144-3p were the most decreased miRNAs in OS. [score:4]
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11
[+] score: 11
Akin to the results obtained for the other members of that cluster high expression was noted only in the same four cell lines with 19q13 rearrangements expressing miR-512-5p, miR-517a, and miR-519a (Figure 3a) whereas a significantly lower expression was seen in the remaining cell lines (p = 0.001659; for details see Table 2). [score:7]
To evaluate the role of either of the two miRNA clusters located in close proximity to the breakpoint region as possible targets of the 19q13 translocations in thyroid adenomas, we have first used to compare the expression of three members of the C19MC cluster, i. e. miR-512-5p, miR-517a, and miR-519a in five cell lines established from thyroid adenomas with 19q13 rearrangements and three cell lines from adenomas with other clonal abnormalities (Table 1). [score:3]
miR-512-1 (pre-miR) is coding for mature-miR-512-5p, miR-371 (pre-miR) is coding for mature-miR371-3p. [score:1]
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12
[+] 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-18a, hsa-mir-22, hsa-mir-29a, hsa-mir-30a, hsa-mir-93, hsa-mir-100, 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-30b, mmu-mir-124-3, mmu-mir-126a, mmu-mir-9-2, mmu-mir-133a-1, mmu-mir-146a, mmu-mir-200b, mmu-mir-203, mmu-mir-204, mmu-mir-205, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-10a, hsa-mir-34a, hsa-mir-203a, hsa-mir-204, hsa-mir-205, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-221, hsa-mir-222, hsa-mir-200b, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-30b, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-126, hsa-mir-146a, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-148a, 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-18a, mmu-mir-22, mmu-mir-29a, mmu-mir-29c, mmu-mir-93, mmu-mir-34a, hsa-mir-200c, hsa-mir-1-1, mmu-mir-1a-2, mmu-mir-10a, mmu-mir-100, mmu-mir-200c, mmu-mir-218-1, mmu-mir-218-2, mmu-mir-221, mmu-mir-222, mmu-mir-29b-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-34b, hsa-mir-34c, hsa-mir-30e, hsa-mir-375, mmu-mir-375, hsa-mir-335, mmu-mir-335, mmu-mir-133a-2, hsa-mir-424, hsa-mir-193b, hsa-mir-512-2, hsa-mir-515-1, hsa-mir-515-2, hsa-mir-518f, hsa-mir-518b, hsa-mir-517a, hsa-mir-519d, hsa-mir-516b-2, hsa-mir-516b-1, hsa-mir-517c, hsa-mir-519a-1, hsa-mir-516a-1, hsa-mir-516a-2, hsa-mir-519a-2, hsa-mir-503, mmu-mir-503, hsa-mir-642a, mmu-mir-190b, mmu-mir-193b, hsa-mir-190b, mmu-mir-1b, hsa-mir-203b, mmu-let-7j, mmu-mir-30f, mmu-let-7k, mmu-mir-126b, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
Significant expression of miRNAs within this cluster (miR-512-3p, miR-512-5p, mir-515-5p, miR-516b, miR-517a, miR-517c, miR-518b, miR-518f, miR-519a and miR-519d) was observed in the MaSC/basal population (Fig.   3b), whereas no highly expressed luminal-specific primate miRNAs were identified. [score:5]
Moreover, miR-512 has been implicated in targeting the pro-survival gene MCL-1 that is expressed at very low levels in this subset [66]. [score:5]
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[+] score: 9
The expression of miR-181c, miR-212 and miR-512 was silenced with DNA hypermethylation in gastric cancer, and their restored expression could induce decreased gastric cancer cell growth via inhibition of oncogenes expression (Refs 81, 82, 83). [score:9]
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[+] score: 9
Other miRNAs from this paper: hsa-mir-320a, hsa-mir-196b, hsa-mir-512-2, hsa-mir-708, hsa-mir-1246
Recent data have indicated that the inhibition of c-FLIP expression by miR-512-3p contributes to taxol -induced apoptosis in hepatocellular carcinoma cells [19]. [score:5]
For example, miRNA-512-3p has been shown to regulate c-FLIP expression in hepatocellular carcinoma cells [19]. [score:4]
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15
[+] score: 9
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-130a, 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-512-2, 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
For example, the cluster of miR-512-3p, miR-205, and the miR-302 family illustrated on the heat map demonstrates high expression in undifferentiated ES and early neural progenitor stages, downregulation during the glial restricted and early OP transitions, but then additional high expression during mid to late OP development. [score:9]
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16
[+] score: 9
Chromatin remo deling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells. [score:4]
Activation of miR-512-5p by epigenetic treatment induced apoptosis of human gastric cancer cell lines via suppression of the MCL1 gene (Saito et al., 2009). [score:3]
miR127, miR-342, and miR-512-5p, are regulated epigenetically (Saito et al., 2013). [score:2]
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17
[+] score: 9
Other miRNAs from this paper: hsa-mir-512-2
Chen F. Zhu H. H. Zhou L. F. Wu S. S. Wang J. Chen Z. Inhibition of c-FLIP expression by miR-512-3p contributes to taxol -induced apoptosis in hepatocellular carcinoma cellsOncol. [score:5]
Furthermore, downregulation of c-FLIP by a specific microRNAs (i. e., miR-512-3p) increased taxol -induced apoptosis [211], supporting our previous report that silencing c-FLIP variants increases Taxol-triggered apoptosis [7]. [score:4]
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[+] score: 8
Chromatin remo deling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells. [score:4]
Activation of miR-512-5p by epigenetic treatment induces suppression of MCL1, resulting in apoptosis of gastric cancer cells (Saito et al., 2009b). [score:3]
We have also demonstrated that treatment of gastric cancer cells with 5-Aza-CdR and PBA induces activation of miR-512-5p which is located at Alu repeats on chromosome 19. [score:1]
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19
[+] score: 7
The most upregulated miRNA in response to TSP-1 was miR-512-3p, while the most downregulated miRNA was miR-25-5p. [score:7]
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20
[+] score: 5
MiR-512-3p facilitated paclitaxel -induced apoptosis mediated by death receptor (DR) through directly targeting cellular FLICE-like inhibitory protein (c-FLIP) in hepatocellular carcinoma cells [53]. [score:5]
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21
[+] score: 5
Other miRNAs from this paper: hsa-mir-512-2
Knockdown of XIST exerted tumor-suppressive functions by up -regulating miR-512 [27]. [score:5]
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22
[+] score: 5
Other miRNAs from this paper: hsa-mir-512-2
Li, J., Lei, H., Xu, Y. & Tao, Z. Z. miR-512-5p Suppresses Tumor Growth by Targeting hTERT in Telomerase Positive Head and Neck Squamous Cell Carcinoma In Vitro and In Vivo. [score:5]
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23
[+] score: 5
Other miRNAs from this paper: hsa-mir-29a, hsa-mir-512-2, hsa-mir-498, hsa-mir-532, hsa-mir-3064
miR-512-5p suppresses tumor growth by targeting hTERT in telomerase positive head and neck squamous cell carcinoma in vitro and in vivo. [score:5]
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24
[+] score: 4
This result is consistent with available data on some of the targets of altered miRNAs, such as miR-1204, which is related to cell death induction, miR-491-5p, which is a negative regulator of p53 and Bcl-XL, and miR-512-5p, which represses nucleotide -binding oligomerization domain containing 2 (NOD2). [score:4]
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25
[+] score: 4
For instance, miR-512-3p could target PPP3R1 to regulate trophoblast invasion (6). [score:4]
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26
[+] score: 4
Other miRNAs from this paper: hsa-mir-34a, hsa-mir-127, hsa-mir-34b, hsa-mir-34c, hsa-mir-512-2
Activation of miR-512-5p by epigenetic treatment induces suppression of MCL1, resulting in apoptosis of gastric cancer cells [16]. [score:3]
We have also demonstrated that treatment of gastric cancer cells with 5-Aza-CdR and PBA induces activation of miR-512-5p which is located at Alu repeats on chromosome 19. [score:1]
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27
[+] score: 4
Other miRNAs from this paper: hsa-mir-132, hsa-mir-512-2
[39] In addition, other factors, such as miR-512-5p, [37] miR-132/212, [38] and N-myc downstream regulated gene 1, [41] were reported to control p21 expression in a p53-independent manner. [score:4]
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[+] score: 3
Eigenvectors with absolute values greater than 2 are shown in Table 2. Most of the listed miRNAs are members of the miR-302 cluster and two human-specific C19MC clusters (the miR-371/372/373 and miR-512∼ clusters), and these miRNAs were previously reported to be expressed in ES and iPS cells [10], [12]– [16], [30], [31]. [score:3]
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[+] score: 3
0076560.g003 Figure 3 (A) A549 cells were mock infected, infected with A/WSN/33 (5 pfu/cell), or infected after transfection with an equimolar mixture of miRNAs (50nM final concentration) that included either hsa-miR-141, hsa-miR-374b, hsa-miR-449b, hsa-miR-518b, and hsa-miR-1263 (G1), or hsa-miR-147b, hsa-miR-190b, hsa-miR-199a-5p, hsa-miR-512-5p, and hsa-miR-874 (G2). [score:1]
Transfections were performed using the following miRNA specific mimics at a final concentration of 50nM: miR-141, miR-147b, miR-190b, miR-199a-5p, miR-374b, miR-449b, miR-512-5p, miR-518b, miR-874, and miR-1263 (Thermo Scientific/Dharmacon). [score:1]
Ten highly inducible miRNAs (miR-141, miR-147b, miR-190b, miR-199a-5p, miR-374b, miR-449b, miR-512-5p, miR-518b, miR-874, and miR-1263) were used in this experiment and divided randomly into two groups of 5 for analysis: one group (G1) consisted of miR-141, miR-374b, miR-449b, miR-518b, and miR-1263, and the other group (G2) consisted of miR-147b, miR-190b, miR-199a-5p, miR-512-5p, and miR-874 (Figure 3A). [score:1]
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[+] score: 2
Strongest regulation was observed for miR-519d, miR-512-3p and miR-1293 (Fig. 3C). [score:2]
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[+] score: 2
However, the authors did not further analyze the miR-512-5p methylation status in GC. [score:1]
Saito et al (69) reported that miR-512-5p became activated following epigenetic treatment of gastric cancer cells with 5-aza-CdR and 4-phenylbutyric acid, which indicates that miR-512-5p may be inactivated by DNA methylation. [score:1]
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[+] score: 2
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-16-1, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-32, hsa-mir-33a, hsa-mir-96, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-16-2, hsa-mir-192, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-204, hsa-mir-211, hsa-mir-212, hsa-mir-181a-1, hsa-mir-214, hsa-mir-217, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-27b, hsa-mir-122, hsa-mir-125b-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-137, hsa-mir-138-2, hsa-mir-145, hsa-mir-152, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-136, hsa-mir-138-1, hsa-mir-146a, hsa-mir-150, hsa-mir-185, hsa-mir-193a, hsa-mir-194-1, hsa-mir-320a, hsa-mir-155, hsa-mir-181b-2, hsa-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-34c, hsa-mir-26a-2, hsa-mir-302b, hsa-mir-369, hsa-mir-375, hsa-mir-378a, hsa-mir-328, hsa-mir-335, hsa-mir-133b, hsa-mir-409, hsa-mir-484, hsa-mir-485, hsa-mir-486-1, hsa-mir-490, hsa-mir-495, hsa-mir-193b, hsa-mir-497, hsa-mir-512-2, hsa-mir-506, hsa-mir-509-1, hsa-mir-532, hsa-mir-92b, hsa-mir-548a-1, hsa-mir-548b, hsa-mir-548a-2, hsa-mir-548a-3, hsa-mir-548c, hsa-mir-33b, hsa-mir-548d-1, hsa-mir-548d-2, hsa-mir-1224, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-802, hsa-mir-509-2, hsa-mir-509-3, 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-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-548q, hsa-mir-548s, hsa-mir-378b, hsa-mir-548t, hsa-mir-548u, hsa-mir-548v, hsa-mir-548w, hsa-mir-320e, hsa-mir-548x, hsa-mir-378c, hsa-mir-4262, hsa-mir-548y, hsa-mir-548z, hsa-mir-548aa-1, hsa-mir-548aa-2, hsa-mir-548o-2, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-548h-5, hsa-mir-548ab, hsa-mir-378f, hsa-mir-378g, 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-378h, hsa-mir-548ai, hsa-mir-548aj-1, hsa-mir-548aj-2, hsa-mir-548x-2, hsa-mir-548ak, hsa-mir-548al, hsa-mir-378i, hsa-mir-548am, hsa-mir-548an, hsa-mir-203b, 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-378j, hsa-mir-548ay, hsa-mir-548az, hsa-mir-486-2, hsa-mir-548ba, hsa-mir-548bb, hsa-mir-548bc
Patients with alcoholic cardiomyopathy showed changes in several microRNAs (miR-138, miR-485-5p, miR-506, miR-512-5p, miR-548-3p, and miR-4262) and suggested to be involved in the development of cardiac dysfunction [171]. [score:2]
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[+] score: 1
On the other hand, only 4 miRNAs were differentially incremented (miR-512-5p, miR-218-5p, miR-449a and miR-1) with no differentially decreased miRNAs in cells exposed to 12 Gy (Figure 5B and Table 2). [score:1]
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79 ** hsa-mir-365 7.13 *** 77.53 *** hsa-mir-429 54.63 *** 85.25 *** hsa-mir-454 33.25 *** 87.31 - hsa-mir-455-3p 42.76 *** 96.4 - hsa-mir-484 4.83 *** 78.73 - hsa-mir-485-3p 4.75 *** 71.49 *** hsa-mir-501-3p 69.25 *** 91.25 *** hsa-mir-512-5p 21.37 *** 72.89 *** hsa-mir-532-3p 9.5 *** 85.93 *** hsa-mir-541 69.87 *** 97.77 - hsa-mir-600 35.63 *** 93.48 - hsa-mir-625* 28.5 *** 72.89 *** Hits of functional screen Relative percentage of myotubes 1, % of control p value, Mann Whitney test Relative cell count 2, % of control p value, Mann Whitney test hsa-mir-636 2.37 *** 81.98 *** hsa-mir-663 21.38 *** 84.73 *** hsa-mir-664 7.13 *** 82.85 *** hsa-mir-766 45.13 *** 73. [score:1]
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[+] score: 1
Liu et al. [87] recently identified a panel of seven miRNAs that distinguished ALK [+] from ALK [−] ALCLs (miR-512-3p, miR-886-5p, miR-886-3p, miR-708, miR-135b, miR-146a and miR-155), although the biological consequences of these patterns remain largely unknown. [score:1]
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[+] score: 1
Adi Harel S, Bossel Ben-Moshe N, Aylon Y, Bublik DR, Moskovits N, Toperoff G, et al. Reactivation of epigenetically silenced miR-512 and miR-373 sensitizes lung cancer cells to cisplatin and restricts tumor growth. [score:1]
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[+] score: 1
Other miRNAs from this paper: hsa-mir-17, hsa-mir-28, hsa-mir-223, hsa-mir-127, hsa-mir-188, hsa-mir-194-1, hsa-mir-155, hsa-mir-194-2, hsa-mir-30e, hsa-mir-362, hsa-mir-363, hsa-mir-367, hsa-mir-379, hsa-mir-196b, hsa-mir-450a-1, hsa-mir-431, ssc-mir-28, hsa-mir-493, hsa-mir-512-2, hsa-mir-500a, hsa-mir-501, hsa-mir-502, hsa-mir-450a-2, hsa-mir-513a-1, hsa-mir-513a-2, hsa-mir-506, hsa-mir-508, hsa-mir-509-1, hsa-mir-532, hsa-mir-615, hsa-mir-660, bta-mir-127, bta-mir-30e, bta-mir-17, bta-mir-450a-2, bta-mir-532, bta-mir-363, bta-mir-660, hsa-mir-891a, hsa-mir-892a, hsa-mir-509-2, hsa-mir-450b, hsa-mir-892b, hsa-mir-708, hsa-mir-509-3, hsa-mir-1285-1, hsa-mir-1285-2, hsa-mir-1248, ssc-mir-17, bta-mir-155, bta-mir-188, bta-mir-194-2, bta-mir-196b, bta-mir-223, bta-mir-28, bta-mir-362, bta-mir-367, bta-mir-379, bta-mir-431, bta-mir-493, bta-mir-500, bta-mir-502a-1, bta-mir-502a-2, bta-mir-502b, bta-mir-615, bta-mir-708, bta-mir-1248-1, bta-mir-1248-2, ssc-mir-450a, bta-mir-2320, bta-mir-1388, bta-mir-194-1, bta-mir-450a-1, eca-mir-30e, eca-mir-367, eca-mir-684, eca-mir-196b, eca-mir-615, eca-mir-708, eca-mir-194-1, eca-mir-493a, eca-mir-17, eca-mir-1248, eca-mir-28, eca-mir-127, eca-mir-379, eca-mir-431, eca-mir-493b, eca-mir-155, eca-mir-194-2, eca-mir-188, eca-mir-223, eca-mir-362, eca-mir-363, eca-mir-450a, eca-mir-450b, eca-mir-450c, eca-mir-500-1, eca-mir-500-2, eca-mir-501, eca-mir-502, eca-mir-508, eca-mir-509a, eca-mir-532, eca-mir-660, ssc-mir-30e, ssc-mir-196b-1, ssc-mir-450b, ssc-mir-127, ssc-mir-532, ssc-mir-708, ssc-mir-1285, ssc-mir-500, hsa-mir-514b, ssc-mir-363-1, ssc-mir-450c, hsa-mir-500b, ssc-mir-194b, ssc-mir-155, ssc-mir-362, bta-mir-3601, ssc-mir-615, ssc-mir-2320, bta-mir-450b, ssc-mir-194a, ssc-mir-196b-2, ssc-mir-363-2, ssc-mir-493, hsa-mir-892c, eca-mir-1388, eca-mir-514b, eca-mir-506a, eca-mir-509b, bta-mir-194b, ssc-mir-1388, ssc-mir-223, ssc-mir-660, bta-mir-194b-2, bta-mir-1949
The mir-512 cluster is known to be primate specific according to miRBase, and we see no evidence to the contrary. [score:1]
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For example, computational analysis indicated that miRNAs that interact with the CD44 3′-UTR also have binding sites in other matrix encoding mRNA 3′-UTRs, including collagen type 1α1 (Col1α1) repressed by miR-328 and fibronectin type 1 (FN1) repressed by miR-512-3p, miR-491 and miR-671 [19]. [score:1]
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[+] score: 1
By comparison, miRNA transcripts of the C19MC cluster (miR-512, miR-516b, miR-520, and miR-525) were unchanged (Fig. 5). [score:1]
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In another study, they indicated that the CD44 3′UTR is also the ceRNA for collagen type 1α1 (Col1α1) mediated by hsa-miR-328-5p and the ceRNA for fibronectin type 1 (FN1) mediated by hsa-miR-512-3p, hsa-miR-491-5p, and hsa-miR-671-5p [40]. [score:1]
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[+] score: 1
MNPT) miR-449a# 3.92 miR-32 3.49 miR-548c-5p 2.71 miR-562 2.56 miR-103-as 2.53 miR-512-3p 2.41 miR-200c* 2.33 miR-147b 2.24 miR-770-5p 2.09 miR-518c* 2.00 miR-517b 1.88 miR-182 1.79 miR-615-3p 1.70 miR-496 1.59 miR-1200 1.58 miR-375 1.54 miR-551a 1.53 *Passanger strand. [score:1]
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[+] score: 1
Among them, miR-9, miR-148, miR-124, miR-137, miR-34, miR-127 and miR-512 reportedly can be silenced by CpG hypermethylation in at least three types of cancers [6]. [score:1]
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