Downregulation of serum RAB27B confers improved prognosis and is associated with hepatocellular carcinoma progression through PI3K-AKT-P21 signaling

Abstract

Previous study revealed that elevated expression of RAB27B in tissues is correlated with hepatocellular carcinoma (HCC) progression; however, the mechanisms involved in promoting HCC development are still unclear. Moreover, HCC tissues are not readily obtained during routine diagnosis. Therefore, to further explore its potential value in early diagnosis, we examined RAB27B expression in patient sera. First, the correlation between serum RAB27B expression and survival, as well as TNM and Barcelona Clinic Liver Cancer stages, were evaluated in patients with HCC. Second, lentiviral vector plasmids carrying interference sequences and plasmids harboring the complete open reading frame of RAB27B were designed to knockdown or overexpress RAB27B in BEL7402 or HuH-7 cells to determine its biological function. Compared with healthy controls and patients with chronic hepatitis B infection, serum RAB27B was significantly increased in patients with HCC. After down-regulating expression of RAB27B, the proliferation of BEL7402 cells was remarkably inhibited both in vitro and in vivo. Additionally, activation of the PI3K/AKT pathway was significantly diminished. Moreover, cell cycle progression of the knockdown cells was notably arrested in the G1/S phase, and upregulation of p21 contributed to this effect. Restoration experiments to recover RAB27B expression revealed opposing results. These findings indicated RAB27B might regulate cell cycle through the PI3K/AKT/p21 pathway by releasing cytokines via exocytosis, thereby modulating the proliferation of HCC cells. RAB27B could potentially be a valuable serum biomarker for the early diagnosis of, and a therapeutic target in, HCC.