miR-200b suppresses cell proliferation, migration and enhances chemosensitivity in prostate cancer by regulating Bmi-1.
miR-200b suppresses cell proliferation, migration and enhances chemosensitivity in prostate cancer by regulating Bmi-1.
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DOI：
10.3892/or.2013.2897
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发表时间：
2014-02
期刊：
影响因子：
4.2
通讯作者：
Junjie Yu;Youyi Lu;D. Cui;Enhui Li;Yi-ping Zhu;Yu-yang Zhao;Fu-jun Zhao;Shujie Xia
中科院分区：
文献类型：
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作者：
Junjie Yu;Youyi Lu;D. Cui;Enhui Li;Yi-ping Zhu;Yu-yang Zhao;Fu-jun Zhao;Shujie Xia
microRNAs （miRNAs）是一类小的非编码rna，可以转录后调控基因表达，在许多重要的生物学过程中发挥关键作用。mirna在前列腺癌（PCa）发展和发病机制中的作用在很大程度上仍然未知。在本研究中，我们发现miR-200b在临床前列腺肿瘤中与正常前列腺组织相比下调，在晚期PCa细胞系中与正常上皮前列腺细胞相比下调。通过靶向b细胞特异性Moloney小鼠白血病病毒插入位点1 (Bmi-1)， miR-200b的强制表达抑制了PCa细胞的增殖和迁移，并增强了对多西紫杉醇的化学敏感性。在PCa细胞中检测到较高水平的Bmi-1，在PCa细胞中，Bmi-1的敲低与miR-200b过表达的效果相似。此外，我们证实这些效应与E-cadherin和P16水平的升高以及vimentin表达和干细胞标志物（CD44和OCT4）表达的降低有关。这些发现表明，miR-200b通过靶向Bmi-1作为肿瘤抑制因子发挥重要作用，可能是PCa治疗的一个有希望的治疗靶点。
microRNAs (miRNAs) are a class of small non-coding RNAs that can post-transcriptionally regulate gene expression and play critical roles in many important biological processes. The role of miRNAs in prostate cancer (PCa) development and pathogenesis remains largely unknown. In the present study, we showed that miR-200b was downregulated in clinical prostatic tumors when compared to normal prostate tissue and in advanced PCa cell lines when compared to normal epithelial prostatic cells. Enforced miR-200b expression suppressed PCa cell proliferation and migration and enhanced chemosensitivity to docetaxel by targeting B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1). Bmi-1 was detected at higher levels in PCa, and knockdown of Bmi-1 showed similar effects as miR-200b overexpression in PCa cells. Moreover, we confirmed that these effects were correlated with increased levels of E-cadherin and P16 and a reduction in vimentin expression and expression of stem cell markers (CD44 and OCT4). These findings suggest that miR-200b plays vital roles as a tumor-suppressor by targeting Bmi-1 and may be a promising therapeutic target for PCa treatment.