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A novel mutant 10Ala/Arg together with mutant 144Ser/Arg of hepatitis B virus X protein involved in hepatitis B virus-related hepatocarcinogenesis in HepG2 cell lines.
Cancer Lett. 2016 Feb 28; 371(2):285-91.CL

Abstract

Hepatitis B virus (HBV) infection-related hepatocellular carcinoma (HCC) represents a major health problem worldwide. HBV X (HBx) protein is the most common open reading frame that may undergo mutations, resulting in the development of HCC. This study aimed to determine specific HBx mutations that differentiate the central- and para-tumor tissues, and identify their association with HCC development. HBx gene from HCC tumor and para-tumor tissues of 47 HCC patients was amplified, sequenced and statistically analyzed. A novel combination of 2 mutations at residues 10 and 144 was identified which might play a significant role in HCC development. Expression vectors carrying HBx with the specific mutations were constructed and transfected into HepG2 and p53-null HepG2 cells. Compared to wild type (WT) and single mutation of HBx at residue 10 or 144, the 10/144 double mutations strongly up-regulated p21 expression and prolonged G1/S transition in WT- and p53-null HepG2 cells. Apoptosis was also inhibited by HBx harboring 10/44 double-mutation. Binding of 10/144 double-mutant HBx to p53 was lower than WT HBx. Conclusively, the 10/144 double mutation of HBx might play a crucial role in HCC formation.

Authors+Show Affiliations

Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China.Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China; Shandong Cancer Hospital and Institute, Jinan, China.Department of General Surgery, Changping District Hospital, Beijing 102200, China.Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China.Shandong Cancer Hospital and Institute, Jinan, China.Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China.Department of General Surgery, Changping District Hospital, Beijing 102200, China.San Diego Veterans Affairs Medical Center, La Jolla, CA, USA; Division of Infectious Diseases, University of California, San Diego, CA, USA.San Diego Veterans Affairs Medical Center, La Jolla, CA, USA; Division of Infectious Diseases, University of California, San Diego, CA, USA.Department of Infectious Diseases, The Third Hospital of Changzhou, Changzhou Institute of Hepatology, Changzhou City 213001, Jiangsu Province, China. Electronic address: ssewllg@163.com.Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China; Department of Infectious Diseases, The Third Hospital of Changzhou, Changzhou Institute of Hepatology, Changzhou City 213001, Jiangsu Province, China. Electronic address: zhangyulin1968@126.com.Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China. Electronic address: dexi0963@yahoo.com.

Pub Type(s)

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

Language

eng

PubMed ID

26706415

Citation

Shi, Ying, et al. "A Novel Mutant 10Ala/Arg Together With Mutant 144Ser/Arg of Hepatitis B Virus X Protein Involved in Hepatitis B Virus-related Hepatocarcinogenesis in HepG2 Cell Lines." Cancer Letters, vol. 371, no. 2, 2016, pp. 285-91.
Shi Y, Wang J, Wang Y, et al. A novel mutant 10Ala/Arg together with mutant 144Ser/Arg of hepatitis B virus X protein involved in hepatitis B virus-related hepatocarcinogenesis in HepG2 cell lines. Cancer Lett. 2016;371(2):285-91.
Shi, Y., Wang, J., Wang, Y., Wang, A., Guo, H., Wei, F., Mehta, S. R., Espitia, S., Smith, D. M., Liu, L., Zhang, Y., & Chen, D. (2016). A novel mutant 10Ala/Arg together with mutant 144Ser/Arg of hepatitis B virus X protein involved in hepatitis B virus-related hepatocarcinogenesis in HepG2 cell lines. Cancer Letters, 371(2), 285-91. https://doi.org/10.1016/j.canlet.2015.12.008
Shi Y, et al. A Novel Mutant 10Ala/Arg Together With Mutant 144Ser/Arg of Hepatitis B Virus X Protein Involved in Hepatitis B Virus-related Hepatocarcinogenesis in HepG2 Cell Lines. Cancer Lett. 2016 Feb 28;371(2):285-91. PubMed PMID: 26706415.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel mutant 10Ala/Arg together with mutant 144Ser/Arg of hepatitis B virus X protein involved in hepatitis B virus-related hepatocarcinogenesis in HepG2 cell lines. AU - Shi,Ying, AU - Wang,Junwei, AU - Wang,Yuhe, AU - Wang,Anna, AU - Guo,Hongliang, AU - Wei,Feili, AU - Mehta,Sanjay R, AU - Espitia,Stephen, AU - Smith,Davey M, AU - Liu,Longgen, AU - Zhang,Yulin, AU - Chen,Dexi, Y1 - 2015/12/17/ PY - 2015/10/15/received PY - 2015/12/05/revised PY - 2015/12/07/accepted PY - 2017/02/28/pmc-release PY - 2015/12/27/entrez PY - 2015/12/27/pubmed PY - 2016/6/15/medline KW - Hepatitis B virus KW - Hepatocellular carcinoma KW - Mutation SP - 285 EP - 91 JF - Cancer letters JO - Cancer Lett. VL - 371 IS - 2 N2 - Hepatitis B virus (HBV) infection-related hepatocellular carcinoma (HCC) represents a major health problem worldwide. HBV X (HBx) protein is the most common open reading frame that may undergo mutations, resulting in the development of HCC. This study aimed to determine specific HBx mutations that differentiate the central- and para-tumor tissues, and identify their association with HCC development. HBx gene from HCC tumor and para-tumor tissues of 47 HCC patients was amplified, sequenced and statistically analyzed. A novel combination of 2 mutations at residues 10 and 144 was identified which might play a significant role in HCC development. Expression vectors carrying HBx with the specific mutations were constructed and transfected into HepG2 and p53-null HepG2 cells. Compared to wild type (WT) and single mutation of HBx at residue 10 or 144, the 10/144 double mutations strongly up-regulated p21 expression and prolonged G1/S transition in WT- and p53-null HepG2 cells. Apoptosis was also inhibited by HBx harboring 10/44 double-mutation. Binding of 10/144 double-mutant HBx to p53 was lower than WT HBx. Conclusively, the 10/144 double mutation of HBx might play a crucial role in HCC formation. SN - 1872-7980 UR - https://www.unboundmedicine.com/medline/citation/26706415/A_novel_mutant_10Ala/Arg_together_with_mutant_144Ser/Arg_of_hepatitis_B_virus_X_protein_involved_in_hepatitis_B_virus_related_hepatocarcinogenesis_in_HepG2_cell_lines_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(15)00747-8 DB - PRIME DP - Unbound Medicine ER -