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• W623304841 endingPage "1376" @default.
• W623304841 startingPage "1365" @default.
• W623304841 abstract "Previously we found decreased expression of SOCS3 in neointimal hyperplastic region following balloon angioplasty in atherosclerotic micro swine. In our recent in vitro studies using human coronary artery smooth muscle cells (HCASMC), we observed the inhibition of SOCS3 expression in the presence of both TNF-α and IGF-1, correlating with the in vivo findings in microswine. We also reported that two independent mechanisms, JAK/STAT3/NFκB and promoter methylation of SOCS3 were responsible for TNF-α and IGF-1 induced SOCS3 inhibition. In this study, using miRNA array and gene expression approaches, we explored the molecular mechanisms involved in the above SOCS3 repression and identified several miRNAs that are associated with the regulation of SOCS3 expression. Our miRNA expression profiling revealed profound down-regulation of two specific miRNAs, hsa-miR-758 and hsa-miR-1264, whose expression levels were decreased by 8–10 folds in HCASMCs that were treated with both TNF-α and IGF-1. This was accompanied with a significant up-regulation of three specific miRNAs, hsa-miR-155, hsa-miR-146b-5p and hsa-miR-146a, which showed about 3–7 fold increases in their expression levels. Importantly, we also found that the miRNA hsa-miR-1264 targets DNA methyltransferase-1 (DNMT1) transcripts by binding to its 3′UTR region to affect its expression. Expression of hsa-miR-1264 in HCASMCs not only resulted in decreased DNMT1 mRNA transcripts but it also increased SOCS3 expression. The treatment with TNF-α and IGF-1 resulted in drastic decrease in hsa-miR-1264 levels with no change in the expression of DNMT1. Consequently, the DNMT1 activity caused hypermethylation in the CpG island of the SOCS3 promoter region and inhibited its expression. This could be a causative epigenetic mechanism associated with TNF-α and IGF-1 induced smooth muscle cell proliferation involved in the pathogenesis of coronary artery hyperplasia and restenosis." @default.
• W623304841 created "2016-06-24" @default.
• W623304841 creator A5005088993 @default.
• W623304841 creator A5015316781 @default.
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• W623304841 date "2015-06-06" @default.
• W623304841 modified "2023-10-14" @default.
• W623304841 title "Down-regulation of hsa-miR-1264 contributes to DNMT1-mediated silencing of SOCS3" @default.
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• W623304841 doi "https://doi.org/10.1007/s11033-015-3882-x" @default.
• W623304841 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5518648" @default.
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• W623304841 hasPublicationYear "2015" @default.
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