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MiR‐7, Inhibited Indirectly by LincRNA HOTAIR, Directly Inhibits SETDB1 and Reverses the EMTof Breast Cancer Stem Cells

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摘要 : Epithelial‐mesenchymal transition (EMT) contributes to tumor invasion and metastasis in many cancers and correlates highly with the acquisitionof cancer stem cell (CSC) characteristics. EMT also correlates with changesin specific microRNAs (miRNAs) that have already been integrated intotumorigenic programs as either oncogenes or tumor suppressor genes.
Abstract: Epithelial‐mesenchymal transition (EMT) contributes to tumor invasion and metastasis in many cancers and correlates highly with the acquisitionof cancer stem Cell (CSC) characteristics. EMT also correlates with changesin specific microRNAs (miRNAs) that have already been integrated intotumorigenic programs as either oncogenes or tumor suppressor genes.Here we show that miR‐7, which was downregulated in breast cancer stem cells (BCSCs) isolated from the human MCF‐7 and MDA‐MB‐231 cell lines, inhibited cell invasion and metastasis, decreased the BCSC population andpartially reversed EMT in MDA‐MB‐231 cells by directly targeting the oncogene,SETDB1. The conspicuous epigenetic transition induced by miR‐7 overexpression was found not only in MDA‐MB‐231 cells but also in BCSC xenograft tumors. MiR‐7 inhibited the metastasis of BCSCs in lungs, kidneys, and adrenal glands of NOD/sciD mice. ChIP‐PCR result suggested that the SETDB1 induced STAT3 expression by binding to the promoter ofSTAT3. MiR‐7 mediated downregulation of SETDB1 resulted in the suppression of STAT3, which led to the downregulation of c‐myc, twist, and mir‐9. In addition, the downregulation of miR‐7 in BCSCs may be indirectly attributedtolincRNA HOTAIR by modulating the expression of HoxD10 thatpromotes the expression of miR‐7. These findings demonstrate that miR‐7 was a tumor suppressor and that the overexpression of miR‐7 might serve as a good strategy for treating highly invasive breast cancer. 原文链接:http://www.ncbi.nlm.nih.gov/pubmed/25070049 作者:广州赛诚生物 点击:
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