Abstract
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.
Highlights
Hepatocellular carcinoma (HCC), a predominant histological subtype of primary liver cancer, is the fifth deadliest and tenth most common cancer worldwide [1, 2]
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
Twenty candidate genes were chosen for the HCS assay which were highly expressed in SMMC-7721 cells
Summary
Hepatocellular carcinoma (HCC), a predominant histological subtype of primary liver cancer, is the fifth deadliest and tenth most common cancer worldwide [1, 2]. Its prognosis is gloomy with a 5-year survival of 11%. Surgery (e.g. hepatectomy and liver transplantation) provides a potentially curative treatment option for HCC patients. The prognosis remains poor due to high potential metastasis and recurrence. The vast majority of HCC patients are diagnosed at an advanced stage at which surgical treatments are almost impossible [3, 4]. The molecular mechanisms underlying HCC pathogenesis are still poorly understood. Identification of novel prognostic biomarkers and therapeutic targets is of significance to improve the survival of HCC patients
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