MicroRNA-124 inhibits cellular proliferation and invasion by targeting Ets-1 in breast cancer
MicroRNA-124 inhibits cellular proliferation and invasion by targeting Ets-1 in breast cancer
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DOI：
10.1007/s13277-014-2402-2
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发表时间：
2014-11-01
期刊：
影响因子：
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通讯作者：
Zhai, Baoping
中科院分区：
文献类型：
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作者：
Li, Wentao;Zang, Wenqiao;Zhai, Baoping
MicroRNA (miRNA) 是小型非编码 RNA，通过靶向某些信使 RNA (mRNA) 进行翻译抑制或切割，可以调节这些基因的表达。此外，miRNA还可能充当癌基因和抑癌基因，因为miRNA的异常表达与多种人类肿瘤有关。然而，miR-124表达对乳腺癌的影响仍不清楚。本研究旨在研究miR-124在乳腺癌中的表达，特别关注miR-124与乳腺癌细胞MCF-7和MDA-MB-231增殖、侵袭和凋亡的关系。进行实时定量 RT-PCR (qRT-PCR) 来鉴定乳腺癌组织中下调的 miR-124。我们还显示了与淋巴结转移相关的乳腺癌组织中 E26 转化特异性 1 (Ets-1) 和 miR-124 的表达水平。将合成的 miR-124 agomir 转染至 MCF-7 和 MDA-MB-231 中，用 miR-124 处理后，观察到 MCF-7 和 MDA-MB-231 细胞增殖和集落形成潜力显着降低 (P < 0.05)。研究发现，转染 miR-124 agomir 的两种乳腺细胞系的细胞凋亡和迁移率显着较高（P < 0.05）。采用荧光素酶报告基因检测和Western blot验证Ets-1作为miR-124的潜在主要靶基因，结果表明miR-124可以与Ets-1 mRNA 3'非翻译区（UTR）内的推定结合位点结合以降低其表达。基于这些发现，我们提出 miR-124 和 Ets-1 可以作为乳腺癌的治疗剂。
MicroRNAs (miRNAs) are small non-coding RNAs that, by targeting certain messenger RNAs (mRNAs) for translational repression or cleavage, can regulate the expression of these genes. In addition, miRNAs may also function as oncogenes and tumor-suppressor genes, as the abnormal expression of miRNAs is associated with various human tumors. However, the effects of the expression of miR-124 in breast cancer remain unclear. The present study was conducted to study the expression of miR-124 in breast cancer, paying particular attention to miR-124's relation to the proliferation, invasion, and apoptosis in breast cancer cell MCF-7 and MDA-MB-231. Real-time quantitative RT-PCR (qRT-PCR) was performed to identify miR-124 that was down-regulated in breast cancer tissues. We also showed E26 transformation specific-1 (Ets-1) and miR-124 expression levels in breast cancer tissues that were associated with lymph node metastases. With transfected synthetic miR-124 agomir into MCF-7 and MDA-MB-231, a significant reduction (P < 0.05) in MCF-7 and MDA-MB-231 cell proliferation and colony forming potential was observed after treatment with miR-124. Apoptosis and migration rates were found to be significantly higher in two breast-derived cell lines transfected with a miR-124 agomir (P < 0.05). Luciferase reporter assay and Western blot were used to verify Ets-1 as a potential major target gene of miR-124, and the result showed that miR-124 can bind to putative binding sites within the Ets-1 mRNA 3' untranslated region (UTR) to reduce its expression. Based on these findings, we propose that miR-124 and Ets-1 may serve as a therapeutic agent in breast cancer.