miR-634 exhibits anti-tumor activities toward hepatocellular carcinoma via Rab1A and DHX33.
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.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Chris Zhiyi
CZ
Zhang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Yun
Y
Cao
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Jia
J
Fu
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address: yunjp@sysucc.org.cn.
Jing-Ping
JP
Yun
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address: zhangmf@sysucc.org.cn.
Mei-Fang
MF
Zhang
D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D020761:rab1 GTP-Binding Proteins / Q000235:genetics*
D020413:3' Untranslated Regions; C000599270:MIRN-634 microRNA, human; D035683:MicroRNAs; C568925:DHX33 protein, human; D053487:DEAD-box RNA Helicases; D020761:rab1 GTP-Binding Proteins
DHX33; Hepatocellular carcinoma; Metastasis; Rab1A; miR-634
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