Tumor suppressor gene glycine N-methyltransferase and its potential in liver disorders and hepatocellular carcinoma

Marcelo Chen; Ming-Hui Yang; Ming-Min Chang; Yu-Chang Tyan; Yi-Ming Arthur Chen

doi:10.1016/j.taap.2019.114607

Tumor suppressor gene glycine N-methyltransferase and its potential in liver disorders and hepatocellular carcinoma

Toxicol Appl Pharmacol. 2019 Sep 1:378:114607. doi: 10.1016/j.taap.2019.114607. Epub 2019 Jun 3.

Authors

Marcelo Chen¹, Ming-Hui Yang², Ming-Min Chang³, Yu-Chang Tyan⁴, Yi-Ming Arthur Chen⁵

Affiliations

¹ Department of Urology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Cosmetic Applications and Management, Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; School of Medicine, Mackay Medical College, New Taipei City, Taiwan.
² National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Miaoli, Taiwan; Master Program of Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
³ Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴ Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁵ Master Program of Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: mchen4270@gmail.com.

PMID: 31170416
DOI: 10.1016/j.taap.2019.114607

Abstract

Glycine N-methyltransferase is a protein with many functions. In addition to catalyzing the production of sarcosine in the one carbon metabolism pathway, it plays a role in the detoxification of environmental carcinogens such as benzo[a]pyrene, aflatoxin B1, and aristocholic acid. There is also increasing evidence suggesting a role of GNMT deficiency in liver carcinogenesis. In this review, we discuss the role of GNMT in the detoxification of xenobiotics and the mechanism of GNMT suppression during liver tumorigenesis. The protective role of GNMT in the liver allows GNMT to not only serve as a marker of liver disease, but also potentially be applied in the treatment of liver disorders and hepatocellular carcinoma. We describe the potential use of GNMT in gene therapy and we introduce the development of a GNMT promoter reporter assay that can be used to screen medicinal drugs and herbal libraries for natural compounds with anti-cancer properties.

Keywords: Detoxification; Drug screening; Gene therapy; Glycine N-methyltransferase; Hepatocellular carcinoma.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / pathology
Genes, Tumor Suppressor / physiology*
Glycine N-Methyltransferase / genetics*
Humans
Liver / pathology
Liver Neoplasms / genetics*
Liver Neoplasms / pathology
Promoter Regions, Genetic / genetics

Substances

Glycine N-Methyltransferase