High expression of vacuolar protein sorting 4B (VPS4B) is associated with accelerated cell proliferation and poor prognosis in human hepatocellular carcinoma.

Abstract Vacuolar protein sorting 4B (VPS4B) is a member of ATPase family proteins that have been shown to play important roles in the formation of MVBs, virus budding and abscission of cytokinesis. In this study, we investigated the prognostic role of VPS4B in human hepatocellular carcinoma (HCC) and its effect on the growth of HCC cells. Western blot and immunohistochemistrical analyses revealed that VPS4B was significantly upregulated in 98 HCC tissues, compared with adjacent nontumorous samples. Meanwhile, clinicopathological variables and univariate and multivariate survival analyses showed that high VPS4B expression was correlated with multiple clinicopathological factors, including AJCC stage, microvascular invasion, Ki-67 and a poor prognosis. More importantly, univariate and multivariate survival analyses demonstrated that VPS4B served as an independent prognostic factor for survival in HCC patients. Furthermore, we found that VPS4B was lowly expressed in serum-starved Huh7 and HepG2 HCC cells, and was progressively increased after serum-refeeding. To study whether VPS4B could regulate the proliferation of HCC cells, VPS4B was knocked down in both Huh7 and HepG2 cells through the transfection of VPS4B-siRNA oligos. Flow cytometry and CCK-8 assay results indicated that interference of VPS4B led to cell cycle arrest and reduced cell proliferation of HCC cells. Taken together, our results implied that VPS4B could be a candidate prognostic biomarker as well as a potential therapeutical target of HCC.