Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular carcinoma cells via targeting Pyk2
Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular carcinoma cells via targeting Pyk2
复制标题
下调 miR-517a 和 miR-517c 通过靶向 Pyk2 促进肝细胞癌细胞增殖
DOI：
10.1016/j.canlet.2012.10.027
复制
发表时间：
2013-02-28
期刊：
影响因子：
9.7
通讯作者：
Han, Ze-Guang
中科院分区：
文献类型：
--
作者：
Liu, Rui-Fang;Xu, Xiao;Han, Ze-Guang
越来越多的证据表明，一些肿瘤抑制miRNAs在癌发生过程中受到表观遗传修饰。在此，我们发现在用DNA甲基化抑制剂和组蛋白去乙酰化酶抑制剂联合处理后，C19 MC的一个大的miRNA簇在HCC细胞中上调。miR-517 a和miR-517 c与C19 MC中其余41种miRNA显著不同。miR-517 a和miR-517 c的异位表达通过阻断G2/M转换抑制细胞增殖，而miR-517 a和miR-517 c的下调促进细胞生长。我们进一步表明Pyk 2是miR-517 a和miR-517 c的靶点，并且这两种miRNA在HCC样品中下调。这些数据共同表明miR-517 a和miR-517 c的下调通过调节Pyk 2促进HCC的发展。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Growing evidence indicates that some tumor suppressive miRNAs are subject to epigenetic modifications during carcinogenesis. Here, we found that a large miRNA cluster of C19MC was upregulated in HCC cells after combined treatment with DNA methylation inhibitor and histone deacetylase inhibitor. MiR-517a and miR-517c were strikingly different from the remaining 41 miRNAs in C19MC. Ectopic expression of MiR-517a and miR-517c inhibited cell proliferation by blocking G2/M transition, whereas down-regulation of miR-517a and miR-517c facilitated cell growth. We further showed Pyk2 is a target of miR-517a and miR-517c and both the miRNAs are downregulated in HCC samples. These data collectively suggest that down-regulation of both miR-517a and miR-517c contribute to HCC development through regulating Pyk2. (C) 2012 Elsevier Ireland Ltd. All rights reserved.