RAB25 promotes hepatitis B virus-induced liver fibrosis progression through activation of the PI3K/AKT signaling pathway.

Despite the clinical possibility of reducing hepatitis B virus (HBV) to almost undetectable levels through nucleotide analogs or interferon, the process of hepatic fibrosis in HBV hepatitis carriers perdures. This study will investigate the function of RAB25 in HBV-induced liver fibrosis and related mechanisms. In the study, the expression level of RAB25 was shown to be increased within liver fibrotic tissue samples in Gene Expression Omnibus (GEO) microarrays (GSE171294 and GSE84044) and clinical samples as well as in HBV-induced hepatic stellate cells (HSCs) activation. Silencing RAB25 inhibited HSCs activation induced by TGF-β1 and HBV-associated hepatocellular carcinoma cells HepG2.2.15, also significantly inhibited HSCs viability, proliferation, and migration and the expression levels of α-SMA, Collagen I, MMP2, and PCNA. However, the overexpression of RAB25 significantly promoted HBV-associated hepatocellular carcinoma cells and TGF-β1-induced HSCs activation. Mechanistically, silencing RAB25 in HSCs significantly repressed PI3K/AKT activation triggered by HBV-associated hepatocellular carcinoma cells. However, the overexpression of RAB25 notably promoted PI3K/AKT activation. In conclusion, silencing of RAB25 inhibits HBV-associated hepatocellular carcinoma cell-induced hepatic fibrosis by suppressing the PI3K/AKT signaling. RAB25 has been proven to be an underlying target for clinical treatment of HBV-associated liver fibrosis.