Obstetrics and Gynecology Hospital of Fudan University, No. 419, Fangxie Road, Shanghai, PR China.
Oncol Rep. 2012 Feb;27(2):594-8. doi: 10.3892/or.2011.1530. Epub 2011 Nov 8.
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.
微小 RNA（miRNAs）是一类新兴的小调控 RNA，其改变与人类癌症的发生和发展有关。我们的研究表明，miR-25 在临床卵巢癌样本和细胞系中均高度表达。下调卵巢癌细胞中的 miR-25 诱导细胞凋亡，而过表达 miR-25 则增强细胞增殖。miR-25 缺失的作用部分通过内在凋亡途径介导。转染后许多促凋亡蛋白如 Bim、Bax 和 caspase-3 上调。此外，荧光素酶测定表明 Bim 是 miR-25 的直接靶标。引入没有 3'UTR 的 Bim cDNA 可消除 miR-25 诱导的细胞存活。最后，在卵巢癌组织中 Bim 和 miR-25 的表达呈负相关。总之，这些数据表明 miR-25 通过靶向 Bim 直接调节卵巢癌中的细胞凋亡，miR-25 可能是卵巢癌干预的潜在治疗靶点。
