ArticleMolecular oncology2019
Elevated N-methyltransferase expression induced by hepatic stellate cells contributes to the metastasis of hepatocellular carcinoma via regulation of the CD44v3 isoform.
Article in Molecular oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 53 citations in OpenAlex.
- Review
- Article
- Nicotinamide N-methyltransferase as a therapeutic target in taxane-resistant castration-resistant prostate cancer.Cell death discovery · 2026Article
- Increased Glycine-N-methyltransferase expression disrupts light-dependent gene expression rhythms in the Drosophila eye.Journal of cell science · 2026Article
- Histone Methylation: A Pivotal Epigenetic Driver of the Malignant Transformation of MASLD-HCC.Journal of hepatocellular carcinoma · 2026Review
- CD44v6 CAR-T Cells Target DNMT3A-Mutant AML: Synergistic Enhancement by Decitabine.Current medical science · 2025Article
- Statins and adhesion molecules: a review of a novel pleiotropic property of statins.Immunologic research · 2025Review
- Antisense oligonucleotide targeting nicotinamide N-methyltransferase exhibits antitumor effects.Molecular therapy. Nucleic acids · 2025Article
- Nicotinamide N-Methyltransferase (NNMT) and Liver Cancer: From Metabolic Networks to Therapeutic Targets.Biomolecules · 2025Review
- Nicotinamide metabolism reprogramming drives reversible senescence of glioblastoma cells.Cellular and molecular life sciences : CMLS · 2025Article
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- [Strategies of statins for the prevention and treatment of hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Heparan sulfate chains in hepatocellular carcinoma.Gastroenterology report · 2025Review
- Exploring NNMT: from metabolic pathways to therapeutic targets.Archives of pharmacal research · 2024Review
- Linking fatty liver diseases to hepatocellular carcinoma by hepatic stellate cells.Journal of the National Cancer Center · 2024Review
- Review
- Dynamic regulation of EXO1 promotes the progression from liver fibrosis to HCC through TGF-β1/Smad signaling feedback loop.Hepatology communications · 2024Article
- Nicotinamide N-methyltransferase and liver diseases.Genes & diseases · 2023Review
- Nicotinamide N-methyltransferase sustains a core epigenetic program that promotes metastatic colonization in breast cancer.The EMBO journal · 2023Article
- Recent Advances in the Management of Clear Cell Renal Cell Carcinoma: Novel Biomarkers and Targeted Therapies.Cancers · 2023Review
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cross-talk between hepatic stellate cells (HSCs) and hepatic carcinoma cells contributes to hepatocellular carcinoma (HCC) progression, but the underlying mechanism is largely unknown. We report here that activated HSCs induce upregulation of nicotinamide N-methyltransferase (NNMT), which is known to regulate multiple metabolic pathways in hepatoma cells of the liver. High levels of NNMT in HCC tissues were positively correlated with vascular invasion, increased serum HBV-DNA levels, and distant metastasis. In addition, functional assays showed that NNMT promoted HCC cell invasion and metastasis by altering the histone H3 methylation on 27 methylation pattern and transcriptionally activating cluster of differentiation 44 (CD44). NNMT-mediated N6-methyladenosine modification of CD44 mRNA resulted in the formation of a CD44v3 splice variant, while its product 1-methyl-nicotinamide stabilized CD44 protein by preventing ubiquitin-mediated degradation. Finally, NNMT was also shown to be a target of statins that inhibited metastasis of hepatoma cells. Taken together, our study shows for the first time that the NNMT/CD44v3 axis regulates HCC metastasis and presents NNMT as a promising prognostic biomarker and therapeutic target for HCC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.