Rab31 promoted hepatocellular carcinoma (HCC) progression via inhibition of cell apoptosis induced by PI3K/AKT/Bcl-2/BAX pathway

• Published in: Tumor biology 2015-11, Vol.36 (11), p.8661-8670
• Main Authors: Sui, Yanxia, Zheng, Xiaoqiang, Zhao, Dongli
• Format: Article
• Language: English
• Subjects: Adult; Apoptosis; bcl-2-Associated X Protein - genetics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Proliferation - genetics; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Middle Aged; Phosphatidylinositol 3-Kinases - genetics; Proteins; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-bcl-2 - genetics; rab GTP-Binding Proteins - biosynthesis; rab GTP-Binding Proteins - genetics; Research Article; Signal Transduction; Tissues
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-015-3626-5

Rab31 belongs to the Ras superfamily of small GTP-binding proteins, which has been found to regulate the vesicle transport from the Golgi apparatus to early and late endosomes. The investigation here detected the expression of Rab31 in 96 patients with hepatocellular carcinoma (HCC) and tried to identify its significance on outcome of HCCs after liver resection. By immunohistochemistry staining, it was found that Rab31 expression in HCC tissues was remarkably higher than that in adjacent liver tissues. Aberrant Rab31 overexpression in HCC tissues was identified to be associated with worse prognosis after liver resection. Univariate analysis showed that advanced tumor–nodes–metastasis (TNM) staging of HCC, intrahepatic metastases, portal vein invasion, and higher Rab31 were the predictive factors of poor prognosis. Multivariate analysis demonstrated that intrahepatic metastases and higher Rab31 were the independent prognostic factors. Furthermore, forced expression of Rab31 in Huh7 cells was found to promote cell growth via upregulation of Bcl-2/BAX ratio induced by PI3K/AKT. Correspondingly, silencing Rab31 induced cell apoptosis and in turn suppressed the growth capacity of MHCC97 cells in vitro. Taken together, this study provides the evidence of Rab31 overexpression in HCC, and Rab31 is potentially used as a novel biomarker of poor prognosis in patients with HCC. PI3K/AKT/Bcl-2/BAX axis was involved in Rab31-promoting HCC progression.