Up-regulation of human cervical cancer proto-oncogene contributes to hepatitis B virus-induced malignant transformation of hepatocyte by down-regulating E-cadherin
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Junfeng Li1, Xiaopeng Dai1, Hongfei Zhang1, Wei Zhang1, Shihui Sun1, Tongtong Gao1, Zhihua Kou1, Hong Yu1, Yan Guo1, Lanying Du2, Shibo Jiang2,3, Jianying Zhang4, Yusen Zhou1
1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
2Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA
3Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College, Fudan University, Shanghai, China
4Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, USA
Yusen Zhou, e-mail: firstname.lastname@example.org
Keywords: hepatocellular carcinoma, human cervical cancer proto-oncogene, hepatitis B virus, TCF/β-catenin pathway, E-cadherin
Received: March 22, 2015 Accepted: August 25, 2015 Published: September 04, 2015
Hepatocellular carcinoma (HCC) is one of the most fatal human malignancies, Human cervical cancer proto-oncogene (HCCR) aberrantly expressed in a number of malignant tumors, including HCC. HCC is associated with Hepatitis B virus (HBV) infection in a large percentage of cases. To explore the regulation and function of HCCR expression in the development of HCC, we detected HCCR expression in HBV expressing hepatocytes. Results showed that the expression of HCCR was higher in HBV-expressing hepatocytes than that in control cells. Examining different components of HBV revealed that the HBx promotes HCCR expression in hepatocytes via the T-cell factor (TCF)/β-catenin pathway. HCCR expression in HBx transgenic mice increased with as the mice aged and developed tumors. We also found that overexpression of HCCR in hepatocytes promoted cell proliferation, migration, and invasion and reduced cell adhesion. Suppressing HCCR expression abolished the effect of HBx-induced hepatocyte growth. In addition, HCCR represses the expression of E-cadherin by inhibition its promoter activity, which might correlate with the effects of HCCR in hepatocytes. Taken together, these results demonstrate that HBx-HCCR-E-cadherin regulation pathway might play an important role in HBV-induced hepatocarcinogenesis. They also imply that HCCR is a potential risk marker for HCC and/or a potential therapeutic target.
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