ArticleClinical epigenetics2023
Metformin regulates expression of DNA methyltransferases through the miR-148/-152 family in non-small lung cancer cells.
Article in Clinical epigenetics, 2023. 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, 18 citations in OpenAlex.
- Sotagliflozin, a Dual SGLT1/2 Inhibitor, Modulates DNMT1 and Class I/II HDAC Expression in Association With Anticancer Effects in Breast and Lung Cancer Cells.Cell biology international · 2026Article
- Research progress of MicroRNA in lung cancer.Discover oncology · 2026Review
- Article
- Research trends in epigenetic studies on lung cancer: a bibliometric and visual analysis of the past decade.Journal of thoracic disease · 2025Article
- Targeting the molecular crosstalk between diabetes and lung cancer for therapeutic intervention.Discover oncology · 2025Review
- Regulation and function of microRNA-152 in various types of cancers: its upstream regulators and downstream targets.Clinical and experimental medicine · 2025Review
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Epigenetic regulation of the tumor microenvironment in lung cancer: mechanism insights and therapeutic prospects.Frontiers in immunology · 2025Review
- Review
- Non-coding RNAs as potential targets in metformin therapy for cancer.Cancer cell international · 2024Review
- "Crosstalk between non-coding RNAs and transcription factor LRF in non-small cell lung cancer".Non-coding RNA research · 2024Article
- DNMT1/miR-152-3p/SOS1 signaling axis promotes self-renewal and tumor growth of cancer stem-like cells derived from non-small cell lung cancer.Clinical epigenetics · 2024Article
- Metformin as a Potential Therapeutic Agent in Breast Cancer: Targeting miR-125a Methylation and Epigenetic Regulation.International journal of molecular and cellular medicine · 2024Article
- Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- miR-124 as a Liquid Biopsy Prognostic Biomarker in Small Extracellular Vesicles from NSCLC Patients.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTo understand the molecular mechanisms involved in regulation of DNA methyltransferases (DNMTs) by metformin in non-small cell lung cancer (NSCLC) cells.
methodsExpression levels of DNMTs in response to metformin were analyzed in NSCLC cells. MicroRNAs regulating expression of DNMTs at the post-transcriptional level were searched using miRNA-target databases (miRDB and miRTarBase), TCGA RNASeqV2 lung cancer data, and miRNA-seq.
resultsMetformin dose-dependently downregulated expression of DNMT1 and DNMT3a at the post-transcriptional level and expression of DNMT3b at the transcriptional level in A549 lung cancer cells. Activity of DNMTs was reduced by about 2.6-fold in A549 cells treated with 10 mM metformin for 72 h. miR-148/-152 family members (miR-148a, miR-148b, and miR-152) targeting the 3'UTR of DNMTs were associated with post-transcriptional regulation of DNMTs by metformin. Metformin upregulated expression of miR-148a, miR-148b, and miR-152 in A549 and H1650 cells. Transfection with an miR-148b plasmid or a mimic suppressed expression of DNMT1 and DNMT3b in A549 cells. Transfection with the miR-148a mimic in A549 and H1650 cells decreased the luciferase activity of DNMT1 3'UTR. A combination of metformin and cisplatin synergistically increased expression levels of miR-148/-152 family members but decreased expression of DNMTs in A549 cells. Low expression of miR-148b was associated with poor overall survival (HR = 2.56, 95% CI 1.09-6.47; P = 0.04) but not with recurrence-free survival.
conclusionsThe present study suggests that metformin inhibits expression of DNMTs by upregulating miR-148/-152 family members in NSCLC cells.
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