ArticleOncotarget2017
Hyperhomocysteinemia results from and promotes hepatocellular carcinoma via CYP450 metabolism by CYP2J2 DNA methylation.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Nicotinamide N-Methyltransferase (NNMT) and Liver Cancer: From Metabolic Networks to Therapeutic Targets.Biomolecules · 2025Review
- Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers.Molecular and cellular biochemistry · 2025Review
- Comparative study of oxidative stress in cancer patients occupationally exposed to the mixture of pesticides.Discover oncology · 2024Article
- Inhibition of Neddylation Suppresses Osteoclast Differentiation and Function In Vitro and Alleviates Osteoporosis In Vivo.Biomedicines · 2022Article
- Toxic Metabolites and Inborn Errors of Amino Acid Metabolism: What One Informs about the Other.Metabolites · 2022Review
- Elevation of Plasma Homocysteine and Minor Hallucinations in Parkinson's Disease: A Cross-Sectional Study.Behavioural neurology · 2022Article
- Natural Polyphenols in Metabolic Syndrome: Protective Mechanisms and Clinical Applications.International journal of molecular sciences · 2021Review
- Involvement of cytochrome P450 enzymes in inflammation and cancer: a review.Cancer chemotherapy and pharmacology · 2021Review
- Targeting the eicosanoid pathway in hepatocellular carcinoma.American journal of cancer research · 2021Review
- Role of homocysteine in the development and progression of Parkinson's disease.Annals of clinical and translational neurology · 2020Review
- Homocysteine: A novel prognostic biomarker in liver transplantation for alpha-fetoprotein- negative hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2020Article
- Reduction of Polyunsaturated Fatty Acids with Tumor Progression in a Lean Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma Mouse Model.Journal of Cancer · 2020Article
- Homocysteine activates autophagy by inhibition of CFTR expression via interaction between DNA methylation and H3K27me3 in mouse liver.Cell death & disease · 2018Article
- CystathionineBioMed research international · 2018Review
- The metabolism and significance of homocysteine in nutrition and health.Nutrition & metabolism · 2017Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperhomocysteinemia (HHcy) can result from liver disease or dysfunction and further alters intracellular lipid metabolism. Cytochrome P450 (CYP) arachidonic acid epoxygenases are expressed in human cancers and promote cancer metastasis. This study explored the interaction of Hcy and CYP450 metabolism in hepatocellular carcinoma (HCC). The levels of 4-epoxyeicosatrienoic acid (EET) isomers and their generative enzyme CYP2J2 level as well as intracellular Hcy level were higher in 42 cases of HCC than in paired non-tumor tissue. Elevated Hcy-decreased DNA methylation on SP1/AP1 binding motifs and enhancement on the CYP2J2 promoter via ERK1/2 signaling was essential for CYP2J2 upregulation and EET metabolism. Increased Hcy level enhanced the neoplastic cellular phenotype, which was reversed by CYP2J2 knockdown in vitro. Furthermore, tumor growth and size as well as patterns of CYP2J2 expression and DNA demethylation were increased with HHcy in mice induced orthotopically by 2% (wt/wt) L-methionine with or without folate deficiency. Moreover, the effect was attenuated by shRNA knockdown of CYP2J2. Thus, HHcy results from but can also promote hepatocarcingenesis via CYP450-EET metabolism by crosstalk of DNA demethylation of CYP2J2 and ERK1/2 signaling.
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