Oncotarget

Research Papers:

Up-regulation of brain-expressed X-linked 2 is critical for hepatitis B virus X protein-induced hepatocellular carcinoma development

Fuqiang Huang, Pei Cai, Yanan Wang, Xian Zhou, Hongyu Chen, Wenjun Liao, Yilei Mao, Xiaojun Zha, Hongbing Zhang and Zhongdong Hu _

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Oncotarget. 2017; 8:65789-65799. https://doi.org/10.18632/oncotarget.19477

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Abstract

Fuqiang Huang2, Pei Cai2, Yanan Wang2, Xian Zhou2, Hongyu Chen2, Wenjun Liao3, Yilei Mao3, Xiaojun Zha4, Hongbing Zhang2 and Zhongdong Hu1,2

1Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China

2State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

3Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

4Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei, China

Correspondence to:

Zhongdong Hu, email: [email protected]

Keywords: HCC, HBV, HBx, BEX2, osteopontin

Received: March 28, 2017    Accepted: June 28, 2017    Published: July 22, 2017

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 the pathogenesis of HBV-induced HCC. However, the molecular mechanisms of HBx-triggered 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.


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