MiR-25 regulates apoptosis by targeting Bim in human ovarian cancer
MiR-25 regulates apoptosis by targeting Bim in human ovarian cancer
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DOI：
10.3892/or.2011.1530
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发表时间：
2012-02-01
期刊：
影响因子：
4.2
通讯作者：
Zhu, Zhiling
中科院分区：
文献类型：
--
作者：
Zhang, Haiyan;Zuo, Zhi;Zhu, Zhiling
MicroRNAs(MiRNAs)是一类小分子调控RNAs，其改变与人类癌症的发生发展密切相关。我们的研究表明miR-25在卵巢癌临床标本和细胞系中都有高表达。MiR-25基因表达下调可诱导卵巢癌细胞凋亡，而miR-25基因过表达可促进细胞增殖。MiR-25的作用部分是通过内源性的细胞凋亡途径实现的。Bim、Bax、caspase-3等促凋亡蛋白表达上调。此外，荧光素酶分析表明，Bim是miR-25的直接靶标。不含3‘端非编码区的Bim基因可阻断miR-25诱导的细胞存活。Bim与miR-25在卵巢癌组织中的表达呈负相关。综上所述，这些数据表明miR-25通过靶向Bim直接调控卵巢癌中的细胞凋亡，miR-25可能成为卵巢癌干预的潜在治疗靶点。
MicroRNAs (miRNAs) are emerging as a class of small regulatory RNAs whose alterations are implicated in the initiation and progression of human cancers. Our study showed that miR-25 was highly expressed both in clinical ovarian cancer samples and cell lines. Down-regulation of miR-25 in ovarian cancer cells induced apoptosis whereas overexpression of miR-25 enhanced cell proliferation. The effects of miR-25 abrogation were partly mediated by the intrinsic apoptosis pathway. Many pro-apoptotic proteins such as Bim, Bax and caspase-3 were up-regulated after transfection. Furthermore, luciferase assays demonstrated that Bim was the direct target of miR-25. Introducing Bim cDNA without 3'UTR abrogated miR-25-induced cell survival. Finally, there was an inverse relationship between Bim and miR-25 expression in ovarian cancer tissues. Taken together, these data indicate that miR-25 directly regulates apoptosis by targeting Bim in ovarian cancer and that miR-25 could be a potential therapeutic target for ovarian cancer intervention.