ArticleOncogene2017
Metformin alters DNA methylation genome-wide via the H19/SAHH axis.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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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.
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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.
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Who cites it
84 citing papers in PubMed, 150 citations in OpenAlex.
- Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals.Clinical epigenetics · 2018Trial
- Epigenetic modifications in type 2 diabetes mellitus.Hormones (Athens, Greece) · 2026Review
- Dose-Dependent Genome-Wide DNA Methylation Remodeling by Metformin Modulates Doxorubicin Sensitivity in Cardiac Cells.Epigenomes · 2026Article
- Metformin in gastrointestinal cancers and inflammatory bowel disease: Unraveling its mechanisms and therapeutic applications.iScience · 2026Review
- Metabolic reprogramming in sepsis-associated encephalopathy: emerging mechanisms, candidate biomarkers, and future therapeutic directions.Frontiers in medicine · 2026Review
- Tissue Iron Predicts Metformin Responsiveness in a Mouse Model and in Humans with Type 2 Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Article
- Type 2 diabetes impacts DNA methylation in human sperm.Clinical epigenetics · 2025Article
- Unravelling the association between metformin and pan-cancers: Mendelian randomization combined with NHANES database analysis.Discover oncology · 2025Article
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- The Research Progress of Metformin Regulation of Metabolic Reprogramming in Malignant Tumors.Pharmaceutical research · 2024Review
- Emodin induces ferroptosis in colorectal cancer through NCOA4-mediated ferritinophagy and NF-κb pathway inactivation.Apoptosis : an international journal on programmed cell death · 2024Article
- Non-coding RNAs as potential targets in metformin therapy for cancer.Cancer cell international · 2024Review
- LncRNAs are involved in regulating ageing and age-related disease through the adenosine monophosphate-activated protein kinase signalling pathway.Genes & diseases · 2024Review
- Mechanistic Insights on Metformin and Arginine Implementation as Repurposed Drugs in Glioblastoma Treatment.International journal of molecular sciences · 2024Article
- Paternal Use of Metformin During the Sperm Development Period Preceding Conception and Risk for Major Congenital Malformations in Newborns.Annals of internal medicine · 2024Article
- The impact of metformin on survival in diabetic endometrial cancer patients: a retrospective population-based analysis.Journal of diabetes and metabolic disorders · 2024Article
- Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.Biology · 2024Review
- Dietary restriction in senolysis and prevention and treatment of disease.Critical reviews in food science and nutrition · 2024Review
- The mechanisms of action of metformin on head and neck cancer in the pre-clinical setting: a scoping review.Frontiers in oncology · 2024Article
24 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
11 authors at 7 institutions in 3 countries.
Funding
Abstract
The molecular mechanisms underlying the antineoplastic properties of metformin, a first-line drug for type 2 diabetes, remain elusive. Here we report that metformin induces genome-wide alterations in DNA methylation by modulating the activity of S-adenosylhomocysteine hydrolase (SAHH). Exposing cancer cells to metformin leads to hypermethylation of tumor-promoting pathway genes and concomitant inhibition of cell proliferation. Metformin acts by upregulating microRNA let-7 through AMPK activation, leading to degradation of H19 long noncoding RNA, which normally binds to and inactivates SAHH. H19 knockdown activates SAHH, enabling DNA methyltransferase 3B to methylate a subset of genes. This metformin-induced H19 repression and alteration of gene methylation are recapitulated in endometrial cancer tissue samples obtained from patients treated with antidiabetic doses of metformin. Our findings unveil a novel mechanism of action for the drug metformin with implications for the molecular basis of epigenetic dysregulation in cancer. This novel mechanism of action also may be occurring in normal cells.
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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.