X-linked 2 and HBV

Oncotarget, 2017, Vol. 8, (No. 39), pp: 65789-65799

ABSTRACT
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death
worldwide. Chronic hepatitis B virus (HBV) infection is a major cause for HCC. Hepatitis
B virus X (HBx), one of four proteins encoded by HBV genome, plays a vital role in北京协和医院肝脏外科毛一雷
the pathogenesis of HBV-induced HCC. However, the molecular mechanisms of HBxtriggered
HCC remain largely undetermined. Here we revealed that the expression
of Brain-expressed X-linked 2 (BEX2) and Osteopontin (OPN) were elevated in liver
tissues of HBV transgenic mice and human HCC specimens. Moreover, a positive
correlation between BEX2 and OPN was exhibited in samples from HCC patients with
HBV infection. The protein levels of BEX2 and OPN were both higher in HBV-positive
HCC specimens compared to that of HBV-negative HCC specimens. HBx potentiated
OPN expression through up-regulation of BEX2. Importantly, the depletion of BEX2
suppressed tumorigenic potential of HCC cells with highly expressed HBx. We
demonstrated the important role of BEX2 in HCC pathogenesis, and BEX2 may be a
novel therapeutic target for HCC patients with HBV infection. The newly identified HBx/
BEX2/OPN signaling cassette is implicated in the pathogenesis of HBV-induced HCC.