ArticleToxicological sciences : an official journal of the Society of Toxicology2019
Gene Expression and DNA Methylation Alterations in the Glycine N-Methyltransferase Gene in Diet-Induced Nonalcoholic Fatty Liver Disease-Associated Carcinogenesis.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Sulfur amino acid restriction prevents S-adenosylmethionine-driven liver steatosis, hepatocellular carcinoma, and metabolic remodeling in high-fat-fed GNMT-null mice.bioRxiv : the preprint server for biology · 2026Article
- Association of Epigenetic Aging Biomarkers With Risk of MASLD-Related HCC.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- DNA methylation of ACADS promotes immunogenic cell death in hepatocellular carcinoma.Cell & bioscience · 2025Article
- Development of a Novel four-gene Model for Monitoring the Progression from Metabolic Dysfunction-associated Steatotic Liver Disease to Hepatocellular Carcinoma in Males.Journal of Cancer · 2025Article
- Epigenetic Modulation with 5-Aza-CdR Prevents Metabolic-Associated Fatty Liver Disease Promoted by Maternal Overnutrition.Nutrients · 2024Article
- Review
- Global DNA methylation and telomere length as markers of accelerated aging in people living with HIV and non-alcoholic fatty liver disease.BMC genomics · 2023Article
- DNA methylation markers in the detection of hepatocellular carcinoma.European journal of cancer (Oxford, England : 1990) · 2023Review
- Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies.Cancers · 2022Review
- Article
- Review
- DNA Methylation Patterns According to Fatty Liver Index and Longitudinal Changes from the Korean Genome and Epidemiology Study (KoGES).Current issues in molecular biology · 2022Article
- Integrated analysis of differentially expressed genes, differentially methylated genes, and natural compounds in hepatitis C virus-induced cirrhosis.The Journal of international medical research · 2022Article
- Dietary Patterns Influence Target Gene Expression through Emerging Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease.Biomedicines · 2021Review
- DNA Methylation in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2020Review
- Aberrant DNA methylation results in altered gene expression in non-alcoholic steatohepatitis-related hepatocellular carcinomas.Journal of cancer research and clinical oncology · 2020Article
- Regulatory Mechanisms of Coicis Semen on Bionetwork of Liver Cancer Based on Network Pharmacology.BioMed research international · 2020Article
- Exploring DNA Methylation Profiles Altered in Cryptogenic Hepatocellular Carcinomas by High-Throughput Targeted DNA Methylation Sequencing: A Preliminary Study for Cryptogenic Hepatocellular Carcinoma.OncoTargets and therapy · 2020Article
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- Review
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming a major etiological risk factor for hepatocellular carcinoma (HCC) in the United States and other Western countries. In this study, we investigated the role of gene-specific promoter cytosine DNA methylation and gene expression alterations in the development of NAFLD-associated HCC in mice using (1) a diet-induced animal model of NAFLD, (2) a Stelic Animal Model of nonalcoholic steatohepatitis-derived HCC, and (3) a choline- and folate-deficient (CFD) diet (CFD model). We found that the development of NAFLD and its progression to HCC was characterized by down-regulation of glycine N-methyltransferase (Gnmt) and this was mediated by progressive Gnmt promoter cytosine DNA hypermethylation. Using a panel of genetically diverse inbred mice, we observed that Gnmt down-regulation was an early event in the pathogenesis of NAFLD and correlated with the extent of the NAFLD-like liver injury. Reduced GNMT expression was also found in human HCC tissue and liver cancer cell lines. In in vitro experiments, we demonstrated that one of the consequences of GNMT inhibition was an increase in genome methylation facilitated by an elevated level of S-adenosyl-L-methionine. Overall, our findings suggest that reduced Gnmt expression caused by promoter hypermethylation is one of the key molecular events in the development of NAFLD-derived HCC and that assessing Gnmt methylation level may be useful for disease stratification.
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