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World J Hepatol. Oct 27, 2018; 10(10): 645-661
Published online Oct 27, 2018. doi: 10.4254/wjh.v10.i10.645
Aberrant expression of alternative isoforms of transcription factors in hepatocellular carcinoma
Olga Krivtsova, Anna Makarova, Natalia Lazarevich
Olga Krivtsova, Anna Makarova, Natalia Lazarevich, Federal State Budgetary Institution, “N. N. Blokhin Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation, Moscow 115478, Russian
Olga Krivtsova, Natalia Lazarevich, M. V. Lomonosov Moscow State University, Moscow 119991, Russian
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 Russian Foundation for Basic Research, contract No. 18-34-00816\18.
Conflict-of-interest statement: All authors declare no potential conflicts of interest related to this manuscript.
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: Natalia Lazarevich, DSc, PhD, Professor, Federal State Budgetary Institution, “N. N. Blokhin Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation, 24/15 Kashirskoye sh., Moscow 115478, Russian. lazarevich.nl@gmail.com
Telephone: +7-499-3235655 Fax: +7-499-3241205
Received: April 20, 2018
Peer-review started: April 21, 2018
First decision: May 8, 2018
Revised: June 8, 2018
Accepted: June 27, 2018
Article in press: June 28, 2018
Published online: October 27, 2018
Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide and the second leading cause of death among all cancer types. Deregulation of the networks of tissue-specific transcription factors (TFs) observed in HCC leads to profound changes in the hepatic transcriptional program that facilitates tumor progression. In addition, recent reports suggest that substantial aberrations in the production of TF isoforms occur in HCC. In vitro experiments have identified distinct isoform-specific regulatory functions and related biological effects of liver-specific TFs that are implicated in carcinogenesis, which may be relevant for tumor progression and clinical outcome. This study reviews available data on the expression of isoforms of liver-specific and ubiquitous TFs in the liver and HCC and their effects, including HNF4α, C/EBPs, p73 and TCF7L2, and indicates that assessment of the ratio of isoforms and targeting specific TF variants may be beneficial for the prognosis and treatment of HCC.

Keywords: Alternative isoforms, Transcription factors, Hepatocellular carcinoma, Alternative splicing, Hepatic differentiation, Personalized treatment

Core tip: This paper aims to analyze existing data on the spectrum of isoforms of liver-specific transcription factors produced in the liver and hepatocellular carcinoma (HCC) and implicated in carcinogenesis, their distinct regulatory functions and subsequent isoform-dependent biological effects which may be relevant for tumor progression and clinical outcomes in HCC patients.