ArticleMolecular therapy oncolytics2020
Insulin and Metformin Control Cell Proliferation by Regulating TDG-Mediated DNA Demethylation in Liver and Breast Cancer Cells.
Article in Molecular therapy oncolytics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 40 citations in OpenAlex.
- Metformin suppresses MEN1-associated pancreatic and pituitary neuroendocrine tumors: evidence from mouse models and clinical data.Endocrine-related cancer · 2026Article
- Differences in DNA Methylation in Genes Involved in Vitamin D Metabolism Are Related to Insulin Requirement in Pregnant Women with Gestational Diabetes Mellitus.International journal of molecular sciences · 2024Article
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- Metformin and its potential influence on cell fate decision between apoptosis and senescence in cancer, with a special emphasis on glioblastoma.Frontiers in oncology · 2024Review
- Dietary restriction in senolysis and prevention and treatment of disease.Critical reviews in food science and nutrition · 2024Review
- The Role of Type 2 Diabetes Mellitus-Related Risk Factors and Drugs in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- Comprehensive analysis of the prognostic value and biological function of TDG in hepatocellular carcinoma.Cell cycle (Georgetown, Tex.) · 2023Article
- Metformin regulates expression of DNA methyltransferases through the miR-148/-152 family in non-small lung cancer cells.Clinical epigenetics · 2023Article
- Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer.Molecules (Basel, Switzerland) · 2023Review
- Insulin Requirement for Gestational Diabetes Control Is Related to Higher Vitamin D Levels up to 1 Year Postpartum: A Prospective Cohort Study.Antioxidants (Basel, Switzerland) · 2022Article
- Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice.International journal of molecular sciences · 2022Article
- Developmental arsenic exposure impairs cognition, directly targets DNMT3A, and reduces DNA methylation.EMBO reports · 2022Article
- Computational investigations on target-site searching and recognition mechanisms by thymine DNA glycosylase during DNA repair process.Acta biochimica et biophysica Sinica · 2022Review
- Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring.Molecular cancer · 2022Review
- miR-21-5p/PRKCE axis implicated in immune infiltration and poor prognosis of kidney renal clear cell carcinoma.Frontiers in genetics · 2022Article
- Metformin Ameliorates Chronic Colitis-Related Intestinal FibrosisFrontiers in pharmacology · 2022Article
- Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer.Frontiers in oncology · 2022Review
- Article
- The base excision repair process: comparison between higher and lower eukaryotes.Cellular and molecular life sciences : CMLS · 2021Review
- Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Type 2 diabetes mellitus (T2DM) is a frequent comorbidity of cancer. Hyperinsulinemia secondary to T2DM promotes cancer progression, whereas antidiabetic agents, such as metformin, have anticancer effects. However, the detailed mechanism for insulin and metformin-regulated cancer cell proliferation remains unclear. This study identified a mechanism by which insulin upregulated the expression of c-Myc, sterol regulatory element-binding protein 1 (SREBP1), and acetyl-coenzyme A (CoA) carboxylase 1 (ACC1), which are important regulators of lipogenesis and cell proliferation. Thymine DNA glycosylase (TDG), a DNA demethylase, was transactivated by c-Myc upon insulin treatment, thereby decreasing 5-carboxylcytosine (5caC) abundance in the SREBP1 promoter. On the other hand, metformin-activated AMP-activated protein kinase (AMPK) increased DNA methyltransferase 3A (DNMT3A) activity to increase 5-methylcytosine (5mC) abundance in the TDG promoter. This resulted in decreased TDG expression and enhanced 5caC abundance in the SREBP1 promoter. These findings demonstrate that c-Myc activates, whereas AMPK inhibits, TDG-mediated DNA demethylation of the SREBP1 promoter in insulin-promoted and metformin-suppressed cancer progression, respectively. This study indicates that TDG is an epigenetic-based therapeutic target for cancers associated with T2DM.
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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.