RAB10 overexpression promotes tumor growth and indicates poor prognosis of hepatocellular carcinoma
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Wei Wang1,*, Wei-Dong Jia2, Bing Hu1, Yue-Yin Pan1,*
1Department of Medical Oncology, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, PR China
2Department of Hepatic Surgery, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, PR China
*These authors contributed equally to this work
Wei Wang, email: firstname.lastname@example.org
Yue-Yin Pan, email: email@example.com
Keywords: RAB10, hepatocellular carcinoma, oncogene, biomarker, therapeutic target
Received: December 08, 2016 Accepted: February 07, 2017 Published: February 19, 2017
Hepatocellular carcinoma (HCC), one of the most common and lethal cancers worldwide, has a high recurrence rate with current treatment modalities. Identifying biomarkers for early diagnosis and discovering new sufficient molecular targets for the development of targeted therapies are urgently needed. RAB10, a member of the RAS family, has been shown to be highly expressed in HCC. However, the function of RAB10 in HCC is less studied. Here we report that RAB10 acts as an oncogene in HCC. The shRNA-mediated knockdown of RAB10 significantly reduced the proliferation of HCC cells and colony formation, induced cell cycle arrest at G0/G1 phase and increased apoptosis in vitro. In addition, RAB10 knockdown suppressed HCC growth in nude mice. Moreover, RAB10 silencing decreased the phosphorylation of InsR, Met/HGFR, Ron/MST1R, Ret, c-Kit/SCFR, EphA3, EphB4, Tyro3/Dtk, Axl, Tie2/TEK, VEGFR2/KDR, Akt/PKB/Rac, S6 Ribosomal Protein and c-Abl, while the phosphorylation of HSP27, p38 MAPK, Chk2 and TAK1 increased significantly. These results suggest that RAB10 regulates cell survival and proliferation through multiple oncogenic, cell stress and apoptosis pathways. More importantly, high RAB10 expression levels in HCC cells correlated with a poor prognosis in HCC patients. Therefore, our findings revealed an oncogenic role for RAB10 in the pathogenesis of HCC and that RAB10 is a potential molecular target or a biomarker for HCC.
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