Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular carcinoma cells via targeting Pyk2

作者：Liu, Rui-Fang; Xu, Xiao; Huang, Jian; Fei, Qian-Lan; Chen, Fei; Li, Yan-Dong; Han, Ze-Guang^*

来源：Cancer Letters, 2013, 329(2): 164-173.

DOI：10.1016/j.canlet.2012.10.027

• Hepatocellular carcinoma
• 5-Aza-2 '-deoxycytidine
• Trichostatin A
• Cell proliferation
• G2/M arrest

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.

• 出版日期2013-2-28
• 单位上海交通大学; 上海人类基因组研究中心; 上海市闵行区中心医院