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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2019; 25(23): 2863-2877
Published online Jun 21, 2019. doi: 10.3748/wjg.v25.i23.2863
Role of epigenetics in transformation of inflammation into colorectal cancer
Zhen-Hua Yang, Yan-Qi Dang, Guang Ji
Zhen-Hua Yang, Yan-Qi Dang, Guang Ji, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Zhen-Hua Yang, Digestive Endoscopy Department, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Author contributions: All authors contributed equally to this paper with regard to conception and design of the research, literature review and analysis, manuscript critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: The 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/
Corresponding author: Guang Ji, MD, PhD, Chief Physician, Director, Doctor, Full Professor, Occupational Physician, Professor, Research Scientist, Teacher, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai 200032, China. jiliver@vip.sina.com
Telephone: +86-21-64385700 Fax: +86-21-64398310
Received: March 2, 2019
Peer-review started: March 2, 2019
First decision: April 16, 2019
Revised: April 24, 2019
Accepted: May 8, 2019
Article in press: May 8, 2019
Published online: June 21, 2019
Abstract

Molecular mechanisms associated with inflammation-promoted tumorigenesis have become an important topic in cancer research. Various abnormal epigenetic changes, including DNA methylation, histone modification, chromatin remodeling, and noncoding RNA regulation, occur during the transformation of chronic inflammation into colorectal cancer (CRC). These changes not only accelerate transformation but also lead to cancer progression and metastasis by activating carcinogenic signaling pathways. The NF-κB and STAT3 signaling pathways play a particularly important role in the transformation of inflammation into CRC, and both are critical to cellular signal transduction and constantly activated in cancer by various abnormal changes including epigenetics. The NF-κB and STAT3 signals contribute to the microenvironment for tumorigenesis through secretion of a large number of pro-inflammatory cytokines and their crosstalk in the nucleus makes it even more difficult to treat CRC. Compared with gene mutation that is irreversible, epigenetic inheritance is reversible or can be altered by the intervention. Therefore, understanding the role of epigenetic inheritance in the inflammation-cancer transformation may elucidate the pathogenesis of CRC and promote the development of innovative drugs targeting transformation to prevent and treat this malignancy. This review summarizes the literature on the roles of epigenetic mechanisms in the occurrence and development of inflammation-induced CRC. Exploring the role of epigenetics in the transformation of inflammation into CRC may help stimulate futures studies on the role of molecular therapy in CRC.

Keywords: Colorectal cancer, Inflammation, DNA methylation, Histone modification, LncRNA, MicroRNAs, Epigenetics

Core tip: Chronic inflammation can promote the occurrence and progression of colorectal cancer (CRC), drawing more attention to the role of pro-inflammatory cytokines and immune cells in this cancer. By regulating the expression of various inflammatory signaling pathways and pro-inflammatory cytokines, epigenetic inheritance not only participates in the transformation of inflammation into CRC, but also facilitates invasion, metastasis, and drug resistance of CRC. Compared with gene mutation that is irreversible, epigenetic inheritance is reversible or can be altered by the intervention. Therefore, the tumor microenvironment can be regulated by modulating epigenetic modifications, which may be novel alternatives to prevent and treat CRC.