MicroRNA-125b Suppressesed Human Liver Cancer Cell Proliferation and Metastasis by Directly Targeting Oncogene LIN28B
MicroRNA-125b Suppressesed Human Liver Cancer Cell Proliferation and Metastasis by Directly Targeting Oncogene LIN28B
复制标题
DOI：
10.1002/hep.23904
复制
发表时间：
2010-11-01
期刊：
影响因子：
13.5
通讯作者：
He, Xianghuo
中科院分区：
文献类型：
--
作者：
Liang, Linhui;Wong, Chun-Ming;He, Xianghuo
microRNA（miRNAs）是一种小的非编码RNA，在人类癌症中可以作为癌基因或肿瘤抑制因子。我们前期的研究表明miR-125 b是肝细胞癌（HCC）患者的预后指标，但其在HCC发生发展中的作用及确切机制尚不清楚。在这里，我们证明了miR-125 b在体外和体内抑制HCC细胞生长。此外，miR-125 b还能增加p21 Cip 1/Waf 1的表达，并使细胞周期阻滞于G1期向S期的转变。此外，miR-125 b抑制HCC细胞的迁移和侵袭。进一步的研究表明，LIN 28 B是HCC细胞中miR-125 b的下游靶标，因为miR-125 b直接结合到LIN 28 B的3'非翻译区，从而降低LIN 28 B的信使RNA和蛋白水平。LIN 28 B的沉默重现了miR-125 b过表达的作用，而LIN 28 B的强制表达逆转了miR-125 b的抑制作用。结论：这些发现表明miR-125 b通过抑制癌基因LIN 28 B的表达在肝癌发生中发挥肿瘤抑制作用，并提示miR-125 b在HCC中的治疗应用。（肝脏学2010;52：1731-1740）
MicroRNAs (miRNAs) are small, noncoding RNAs that can act as oncogenes or tumor suppressors in human cancer. Our previous study showed that miR-125b was a prognostic indicator for patients with hepatocellular carcinoma (HCC), but its functions and exact mechanisms in hepatic carcinogenesis are still unknown. Here we demonstrate that miR-125b suppressed HCC cell growth in vitro and in vivo. Moreover, miR-125b increased p21Cip1/Waf1 expression and arrested cell cycle at G(1) to S transition. In addition, miR-125b inhibited HCC cell migration and invasion. Further studies revealed that LIN28B was a downstream target of miR-125b in HCC cells as miR-125b bound directly to the 3' untranslated region of LIN28B, thus reducing both the messenger RNA and protein levels of LIN28B. Silencing of LIN28B recapitulated the effects of miR-125b overexpression, whereas enforced expression of LIN28B reversed the suppressive effects of miR-125b. Conclusion: These findings indicate that miR-125b exerts tumor-suppressive effects in hepatic carcinogenesis through the suppression of oncogene LIN28B expression and suggest a therapeutic application of miR-125b in HCC. (HEPATOLOGY 2010;52:1731-1740)