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

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.