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miR‐634 exhibits anti‐tumor activities toward hepatocellular carcinoma via Rab1A and DHX33

2016; Elsevier BV; Volume: 10; Issue: 10 Linguagem: Inglês

10.1016/j.molonc.2016.09.001

1878-0261

Chris Zhiyi Zhang, Yun Cao, Jia Fu, Jing‐Ping Yun, Mei-Fang Zhang,

RNA Research and Splicing

Abstract Deregulation of microRNAs contributes to the aberrant growth of hepatocellular carcinoma (HCC). Here, we showed that miR‐634 expression was frequently decreased in HCC. Low miR‐634 expression was significantly associated with larger tumor size, poorer tumor differentiation, advanced TNM stage, vascular invasion, absence of tumor capsule and unfavorable overall survival. Overexpression of miR‐634 markedly attenuated cell viability, colony formation, tumor growth and metastasis, whereas miR‐634 inhibition resulted in the opposite phenotypes. Furthermore, re‐introduction of miR‐634 induced cell apoptosis in vitro and in vivo. Mechanistically, miR‐634 inhibited the expression of Rab1A and DHX33 via directly binding to the 3′‐UTR of both genes. In clinical samples, the expression of Rab1A or DHX33 was reversely correlated with miR‐634. Re‐expression of Rab1A or DHX33 abrogated the miR‐634‐mediated inhibition of cell proliferation and migration. Collectively, our data suggest a tumor suppressor role of miR‐634 in HCC. The newly identified miR‐634/Rab1A or miR‐634/DHX33 axis serves as a potential therapeutic target for the clinical management.