ArticleScientific reports2017
MiRNA-21 mediates the antiangiogenic activity of metformin through targeting PTEN and SMAD7 expression and PI3K/AKT pathway.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- Cardiometabolic Therapies Shape Non-Coding RNA Landscapes in Cardiovascular Fibrosis.Metabolites · 2025Review
- The Role of miRNAs in Chemotherapy-Induced Cardiotoxicity.Biomedicines · 2025Review
- Critical roles of miR-21 in promotions angiogenesis: friend or foe?Clinical and experimental medicine · 2025Review
- Critical roles of miR-21 in promotions angiogenesis: friend or foe?Clinical and experimental medicine · 2025Review
- The role of microRNAs in pregnancies complicated by maternal diabetes.Clinical science (London, England : 1979) · 2024Review
- Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Upregulated MicroRNA-21 Drives the Proliferation of Lymphatic Malformation Endothelial Cells by Inhibiting PDCD4.The Journal of investigative dermatology · 2023Article
- Chitosan/Hyaluronic Acid/MicroRNA-21 Nanoparticle-Coated Smooth Titanium Surfaces Promote the Functionality of Human Gingival Fibroblasts.International journal of nanomedicine · 2022Article
- Treatment with adipose-derived regenerative cells enhances ischemia-induced angiogenesis via exosomal microRNA delivery in mice.Nagoya journal of medical science · 2021Article
- Metformin attenuates synergic effect of diabetes mellitus and Helicobacter pylori infection on gastric cancer cells proliferation by suppressing PTEN expression.Journal of cellular and molecular medicine · 2021Article
- Assessment of cytokines, microRNA and patient related outcome measures in conversion disorder/functional neurological disorder (CD/FND): The CANDO clinical feasibility study.Brain, behavior, & immunity - health · 2021Article
- How metformin affects various malignancies by means of microRNAs: a brief review.Cancer cell international · 2021Review
- Regulation of MethylaseDiabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- MicroRNAs: Important Players in Breast Cancer Angiogenesis and Therapeutic Targets.Frontiers in molecular biosciences · 2021Review
- Deviations in MicroRNA-21 Expression Patterns Identify a Therapeutic Target for Diabetic Wound Healing.Journal of immunobiology · 2021Article
- Metformin: The next angiogenesis panacea?SAGE open medicine · 2021Review
- Metformin: A Novel Weapon Against Inflammation.Frontiers in pharmacology · 2021Review
- Review
- Inhibition of miR-21 Regulates Mutant KRAS Effector Pathways and Intercepts Pancreatic Ductal Adenocarcinoma Development.Cancer prevention research (Philadelphia, Pa.) · 2020Article
- Expression and significance of miR-654-5p and miR-376b-3p in patients with colon cancer.World journal of gastrointestinal oncology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin, an anti-diabetic drug commonly used for type 2 diabetes therapy, is associated with anti-angiogenic effects in conditions beyond diabetes. miR-21 has been reported to be involved in the process of angiogenesis. However, the precise regulatory mechanisms by which the metformin-induced endothelial suppression and its effects on miR-21-dependent pathways are still unclear. Bioinformatic analysis and identification of miR-21 and its targets and their effects on metformin-induced antiangiogenic activity were assessed using luciferase assays, quantitative real-time PCR, western blots, scratch assays, CCK-8 assays and tubule formation assays. In this study, miR-21 was strikingly downregulated by metformin in a time- and dose-dependent manner. miR-21 directly targeted the 3'-UTR of PTEN and SMAD7, and negatively regulated their expression. Overexpression of miR-21 abrogated the metformin-mediated inhibition of endothelial cells proliferation, migration, tubule formation and the TGF-β-induced AKT, SMAD- and ERK-dependent phosphorylations, and conversely, down-regulation of miR-21 aggravated metformin's action and revealed significant promotion effects. Our study broadens our understanding of the regulatory mechanism of miR-21 mediating metformin-induced anti-angiogenic effects, providing important implications regarding the design of novel miRNA-based therapeutic strategies against angiogenesis.
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