MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells #

作者：Xu Teng, Ying Zhu, Yujuan Xiong, Yi-Yuan Ge, Jing‐Ping Yun, Shi‐Mei Zhuang · 发表于：Hepatology · 年份：2009 · DOI：10.1002/hep.22919 · 被引用次数：372 · 研究领域：MicroRNA in disease regulation、Circular RNAs in diseases、Cancer-related Molecular Pathways

UNLABELLED: Growing evidence indicates that deregulation of microRNAs (miRNAs) contributes to tumorigenesis. Down-regulation of miR-195 has been observed in various types of cancers. However, the biological function of miR-195 is still largely unknown. In this study we aimed to elucidate the pathophysiologic role of miR-195. Our results showed that miR-195 expression was significantly reduced in as high as 85.7% of hepatocellular carcinoma (HCC) tissues and in all of the five HCC cell lines examined. Moreover, introduction of miR-195 dramatically suppressed the ability of HCC and colorectal carcinoma cells to form colonies in vitro and to develop tumors in nude mice. Furthermore, ectopic expression of miR-195 blocked G(1)/S transition, whereas inhibition of miR-195 promoted cell cycle progression. Subsequent investigation characterized multiple G(1)/S transition-related molecules, including cyclin D1, CDK6, and E2F3, as direct targets of miR-195. Silencing of cyclin D1, CDK6, or E2F3 phenocopied the effect of miR-195, whereas overexpression of these proteins attenuated miR-195-induced G(1) arrest. In addition, miR-195 significantly repressed the phosphorylation of Rb as well as the transactivation of downstream target genes of E2F. These results imply that miR-195 may block the G(1)/S transition by repressing Rb-E2F signaling through targeting multiple molecules, including cyclin D1, CDK6, and E2F3. CONCLUSION: Our data highlight an important role of miR-195 in cell cycle con...