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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2015; 21(42): 12157-12170
Published online Nov 14, 2015. doi: 10.3748/wjg.v21.i42.12157
Transposon mouse models to elucidate the genetic mechanisms of hepatitis B viral induced hepatocellular carcinoma
Amy P Chiu, Barbara R Tschida, Lilian H Lo, Branden S Moriarity, Dewi K Rowlands, David A Largaespada, Vincent W Keng
Amy P Chiu, Lilian H Lo, Vincent W Keng, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China
Barbara R Tschida, Branden S Moriarity, David A Largaespada, Masonic Cancer Center, Department of Pediatrics, Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, United States
Dewi K Rowlands, Laboratory Animal Services Centre, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong, China
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Supported by Health Medical Research Fund No. 11122171, the Food and Health Bureau, and the Hong Kong SAR Government; the Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR (1-ZVAG, G-YBAY, G-UA94 and 1-ZE19); and the NIH IMVTP grant No. T32 AI083196-04 to Tschida BR.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Vincent W Keng, PhD, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China. vincent.keng@polyu.edu.hk
Telephone: +852-34008728 Fax: +852-23649932
Received: August 12, 2015
Peer-review started: August 13, 2015
First decision: September 11, 2015
Revised: September 18, 2015
Accepted: September 30, 2015
Article in press: September 30, 2015
Published online: November 14, 2015
Processing time: 91 Days and 2.5 Hours
Abstract

The major type of human liver cancer is hepatocellular carcinoma (HCC), and there are currently many risk factors that contribute to this deadly disease. The majority of HCC occurrences are associated with chronic hepatitis viral infection, and hepatitis B viral (HBV) infection is currently a major health problem in Eastern Asia. Elucidating the genetic mechanisms associated with HBV-induced HCC has been difficult due to the heterogeneity and genetic complexity associated with this disease. A repertoire of animal models has been broadly used to study the pathophysiology and to develop potential treatment regimens for HBV-associated HCC. The use of these animal models has provided valuable genetic information and has been an important contributor to uncovering the factors involved in liver malignant transformation, invasion and metastasis. Recently, transposon-based mouse models are becoming more widely used in liver cancer research to interrogate the genome by forward genetics and also used to validate genes rapidly in a reverse genetic manner. Importantly, these transposon-based rapid reverse genetic mouse models could become crucial in testing potential therapeutic agents before proceeding to clinical trials in human. Therefore, this review will cover the use of transposon-based mouse models to address the problems of liver cancer, especially HBV-associated HCC occurrences in Asia.

Keywords: Hepatocellular carcinoma; Hepatitis B virus; Transposable elements; Sleeping Beauty; Forward and reverse genetic screens

Core tip: Hepatocellular carcinoma (HCC) is the major type of primary liver cancer and the risk factors that contribute to its formation are hepatitis viral infection, alcohol consumption, aflatoxin exposure, hemochromatosis, and tyrosinemia. In vivo forward and reverse genetic transposon models have been used to study the genetic mechanisms of HCC, including hepatitis B viral-induced HCC. These animal models provide valuable genetic information and are important contributors to uncovering the factors involved in liver malignant transformation, invasion and metastasis. They could also be used to test potential therapeutic agents before proceeding to clinical trials in humans.