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Up-regulation of human cervical cancer proto-oncogene contributes to hepatitis B virus-induced malignant transformation of hepatocyte by down-regulating E-cadherin.
Oncotarget. 2015 Oct 06; 6(30):29196-208.O

Abstract

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.

Authors+Show Affiliations

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA. Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College, Fudan University, Shanghai, China.Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, USA.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26470691

Citation

Li, Junfeng, et al. "Up-regulation of Human Cervical Cancer Proto-oncogene Contributes to Hepatitis B Virus-induced Malignant Transformation of Hepatocyte By Down-regulating E-cadherin." Oncotarget, vol. 6, no. 30, 2015, pp. 29196-208.
Li J, Dai X, Zhang H, et al. Up-regulation of human cervical cancer proto-oncogene contributes to hepatitis B virus-induced malignant transformation of hepatocyte by down-regulating E-cadherin. Oncotarget. 2015;6(30):29196-208.
Li, J., Dai, X., Zhang, H., Zhang, W., Sun, S., Gao, T., Kou, Z., Yu, H., Guo, Y., Du, L., Jiang, S., Zhang, J., & Zhou, Y. (2015). Up-regulation of human cervical cancer proto-oncogene contributes to hepatitis B virus-induced malignant transformation of hepatocyte by down-regulating E-cadherin. Oncotarget, 6(30), 29196-208. https://doi.org/10.18632/oncotarget.5039
Li J, et al. Up-regulation of Human Cervical Cancer Proto-oncogene Contributes to Hepatitis B Virus-induced Malignant Transformation of Hepatocyte By Down-regulating E-cadherin. Oncotarget. 2015 Oct 6;6(30):29196-208. PubMed PMID: 26470691.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Up-regulation of human cervical cancer proto-oncogene contributes to hepatitis B virus-induced malignant transformation of hepatocyte by down-regulating E-cadherin. AU - Li,Junfeng, AU - Dai,Xiaopeng, AU - Zhang,Hongfei, AU - Zhang,Wei, AU - Sun,Shihui, AU - Gao,Tongtong, AU - Kou,Zhihua, AU - Yu,Hong, AU - Guo,Yan, AU - Du,Lanying, AU - Jiang,Shibo, AU - Zhang,Jianying, AU - Zhou,Yusen, PY - 2015/03/22/received PY - 2015/08/25/accepted PY - 2015/10/17/entrez PY - 2015/10/17/pubmed PY - 2016/8/5/medline KW - E-cadherin KW - TCF/β-catenin pathway KW - hepatitis B virus KW - hepatocellular carcinoma KW - human cervical cancer proto-oncogene SP - 29196 EP - 208 JF - Oncotarget JO - Oncotarget VL - 6 IS - 30 N2 - 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. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/26470691/Up_regulation_of_human_cervical_cancer_proto_oncogene_contributes_to_hepatitis_B_virus_induced_malignant_transformation_of_hepatocyte_by_down_regulating_E_cadherin_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=5039 DB - PRIME DP - Unbound Medicine ER -