ArticleOncogene2018
Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Pooled it
- Trial
- Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals.Clinical epigenetics · 2018Trial
- An Integrative Methylation-Metabolism Gene Signature Defines Prognosis and Immunosuppressive Microenvironment in Prostate Cancer.Chemical biology & drug design · 2026Article
- Impact of metformin-based chemo-radiotherapeutic strategies on breast cancer stemness and autophagy-associated gene expression: evidence from ALDH1A1 and LC3 expression analysis.Molecular biology reports · 2026Article
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- Metformin Impairs Breast Cancer Growth through the Inhibition of PRMT6.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hypoxia facilitates triple-negative breast cancer stem cells enrichment and stemness maintenance through oxidized ataxia telangiectasia mutated-induced one-carbon metabolism.World journal of stem cells · 2026Article
- The Methionine-Mitochondria Axis in Cancer: Metabolic Cross-Talk and Therapeutic Vulnerabilities.Current pharmacology reports · 2026Review
- Metformin and insulin exacerbate one-carbon metabolism deficits in pregnant growth restricted rats and impacts the placenta, fetal liver and pancreas.The Journal of physiology · 2025Article
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- Article
- Metabolic Reprogramming in Respiratory Viral Infections: A Focus on SARS-CoV-2, Influenza, and Respiratory Syncytial Virus.Biomolecules · 2025Review
- Article
- Article
- Mechanisms and rationales of SAM homeostasis.Trends in biochemical sciences · 2025Review
- Glibenclamide targets MDH2 to relieve aging phenotypes through metabolism-regulated epigenetic modification.Signal transduction and targeted therapy · 2025Article
- The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications.Molecules (Basel, Switzerland) · 2025Review
- Young apple polyphenol extract prevents diabetic cognitive dysfunction by promoting TET2-mediated active DNA demethylation in the brain of diabetic mice.Frontiers in nutrition · 2025Article
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anti-diabetic biguanide metformin may exert health-promoting effects via metabolic regulation of the epigenome. Here we show that metformin promotes global DNA methylation in non-cancerous, cancer-prone and metastatic cancer cells by decreasing S-adenosylhomocysteine (SAH), a strong feedback inhibitor of S-adenosylmethionine (SAM)-dependent DNA methyltransferases, while promoting the accumulation of SAM, the universal methyl donor for cellular methylation. Using metformin and a mitochondria/complex I (mCI)-targeted analog of metformin (norMitoMet) in experimental pairs of wild-type and AMP-activated protein kinase (AMPK)-, serine hydroxymethyltransferase 2 (SHMT2)- and mCI-null cells, we provide evidence that metformin increases the SAM:SAH ratio-related methylation capacity by targeting the coupling between serine mitochondrial one-carbon flux and CI activity. By increasing the contribution of one-carbon units to the SAM from folate stores while decreasing SAH in response to AMPK-sensed energetic crisis, metformin can operate as a metabolo-epigenetic regulator capable of reprogramming one of the key conduits linking cellular metabolism to the DNA methylation machinery.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.