miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1
miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1
复制标题
miR-146a 通过靶向 Rac1 作为前列腺癌的肿瘤抑制因子
DOI：
10.1002/pros.22878
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发表时间：
2014-12-01
期刊：
影响因子：
2.8
通讯作者：
Yu, Jianxiu
中科院分区：
文献类型：
--
作者：
Sun, Qian;Zhao, Xian;Yu, Jianxiu
背景miR-146a（miR-146a-5p）已被报道在不同类型的癌症中异常表达，目前关于miR-146a在前列腺癌中的作用的认识仍然有限。 方法通过qRT-PCR和原位杂交检测细胞系和组织中miR-146a的表达水平。分别通过集落形成实验和RTCA实验评估miR-146a对细胞生长和迁移的影响。双荧光素酶测定用于检查 miR-146a 与潜在靶标 3'UTR 之间的结合。 结果我们发现前列腺癌细胞中 miR-146a 的强制过度表达受到抑制，而 miR-146a 的敲低则增加了贴壁依赖性生长、迁移和侵袭。机制研究表明，miR-146a 通过与其 3'UTR 结合来抑制 Rac1 的表达。一致的是，Rac1 的敲低表现出过表达 miR-146a 的抗迁移作用，而 miR-146a 沉默细胞中 Rac1 的敲低则拮抗了沉默 miR-146a 诱导的细胞运动增加。此外，在人类前列腺癌组织中，miR-146a被发现与Rac1呈负相关。结论我们的数据表明，miR-146a通过下调Rac1在前列腺癌中发挥抑制作用。 miR-146a/Rac1 信号轴可能是预防前列腺癌进展的潜在治疗靶点。前列腺 74：1613-1621，2014 年。(c) 2014 年 Wiley 期刊公司。
BACKGROUNDmiR-146a (miR-146a-5p) has been reported to be aberrantly expressed in different types of cancers, the current knowledge about the role of miR-146a in prostate cancer is still limited.METHODSThe expression levels of miR-146a in cell lines and tissues were measured by qRT-PCR and in situ hybridization. Effects of miR-146a on cell growth and migration were evaluated by colony formation assay and RTCA assay, respectively. The dual luciferase assay was used to examine the binding between miR-146a and the 3'UTR of potential targets.RESULTSWe found that enforced over-expression of miR-146a in prostate cancer cells suppressed whereas knockdown of miR-146a increased anchorage-independent growth, migration, and invasion. Mechanistic studies revealed that miR-146a repressed the expression of Rac1 through binding to its 3'UTR. Consistently, knockdown of Rac1 phenocopied the anti-migration effect of overexpressing miR-146a, and knockdown of Rac1 in miR-146a-silencing cells antagonized the increase in cell motility induced by silencing miR-146a. Furthermore, miR-146a was found to be inversely correlated with Rac1 in human prostate cancer tissues.CONCLUSIONSOur data suggest that miR-146a plays a suppressive role in prostate cancer through down-regulation of Rac1. The miR-146a/Rac1 signaling axis may be a potential therapeutic target to prevent prostate cancer progression. Prostate 74: 1613-1621, 2014. (c) 2014 Wiley Periodicals, Inc.