ArticlePloS one2011
Down-regulation of miR-101 in endothelial cells promotes blood vessel formation through reduced repression of EZH2.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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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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Who cites it
52 citing papers in PubMed, 114 citations in OpenAlex.
- Epigenetic regulation in atherosclerosis and its therapeutic potential.Nature reviews. Cardiology · 2026Review
- Histone post-translational modifications in diabetic foot ulcer healing: linking immune dysregulation to tissue repair.Frontiers in immunology · 2026Review
- UHRF1 in endothelial cells is essential for angiogenesis and associated with the activation of pro-angiogenic signaling pathways and expression of endothelial genes.Angiogenesis · 2025Article
- Genetic deletion of microRNA-15a/16-1 in pericytes stimulates cerebral angiogenesis and promotes functional recovery after ischemic stroke.Angiogenesis · 2025Article
- miR-1233-3p Inhibits Angiopoietin-1-Induced Endothelial Cell Survival, Migration, and Differentiation.Cells · 2025Article
- Hypoxia-Induced miR-101 Impairs Endothelial Barrier Integrity Through Altering VE-Cadherin and Claudin-5.Molecular neurobiology · 2024Article
- H3K27Me3 abundance increases fibrogenesis during endothelial-to-mesenchymal transition via the silencing of microRNA-29c.Frontiers in cardiovascular medicine · 2024Article
- MicroRNA-Mediated Regulation of Histone-Modifying Enzymes in Cancer: Mechanisms and Therapeutic Implications.Biomolecules · 2023Review
- Depletion of enhancer zeste homolog 2 (EZH2) directs transcription factors associated with T cell differentiation through epigenetic regulation of Yin Yang 1(YY1) in combating non-small cell lung cancer (NSCLC).Medical oncology (Northwood, London, England) · 2023Article
- Flow-Responsive Noncoding RNAs in the Vascular System: Basic Mechanisms for the Clinician.Journal of clinical medicine · 2022Review
- Potential epigenetic molecular regulatory networks in ocular neovascularization.Frontiers in genetics · 2022Review
- Reciprocal regulation of endothelial-mesenchymal transition by MAPK7 and EZH2 in intimal hyperplasia and coronary artery disease.Scientific reports · 2021Article
- Targeting the epigenome in in-stent restenosis: from mechanisms to therapy.Molecular therapy. Nucleic acids · 2021Review
- MicroRNAs overexpressed in Crohn's disease and their interactions with mechanisms of epigenetic regulation explain novel aspects of Crohn's disease pathogenesis.Clinical epigenetics · 2021Review
- The Endothelium as a Target for Anti-Atherogenic Therapy: A Focus on the Epigenetic Enzymes EZH2 and SIRT1.Journal of personalized medicine · 2021Review
- MiRNAs in Gestational Diabetes Mellitus: Potential Mechanisms and Clinical Applications.Journal of diabetes research · 2021Review
- Regulatory Mechanisms of Epigenetic miRNA Relationships in Human Cancer and Potential as Therapeutic Targets.Cancers · 2020Review
- MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy.Cardiovascular diabetology · 2020Review
- Non-Coding RNA: Role in Gestational Diabetes Pathophysiology and Complications.International journal of molecular sciences · 2020Review
- Endothelium-Targeted Deletion of microRNA-15a/16-1 Promotes Poststroke Angiogenesis and Improves Long-Term Neurological Recovery.Circulation research · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Angiogenesis is a balanced process controlled by pro- and anti-angiogenic molecules of which the regulation is not fully understood. Besides classical gene regulation, miRNAs have emerged as post-transcriptional regulators of angiogenesis. Furthermore, epigenetic changes caused by histone-modifying enzymes were shown to modulate angiogenesis as well. However, a possible interplay between miRNAs and histone-modulating enzymes during angiogenesis has not been described. Here we show that VEGF-mediated down-regulation of miR-101 caused pro-angiogenic effects. We found that the pro-angiogenic effects are partly mediated through reduced repression by miR-101 of the histone-methyltransferase EZH2, a member of the Polycomb group family, thereby increasing methylation of histone H3 at lysine 27 and transcriptome alterations. In vitro, the sprouting and migratory properties of primary endothelial cell cultures were reduced by inhibiting EZH2 through up-regulation of miR-101, siRNA-mediated knockdown of EZH2, or treatment with 3-Deazaneplanocin-A (DZNep), a small molecule inhibitor of EZH2 methyltransferase activity. In addition, we found that systemic DZNep administration reduced the number of blood vessels in a subcutaneous glioblastoma mouse model, without showing adverse toxicities. Altogether, by identifying a pro-angiogenic VEGF/miR-101/EZH2 axis in endothelial cells we provide evidence for a functional link between growth factor-mediated signaling, post-transcriptional silencing, and histone-methylation in the angiogenesis process. Inhibition of EZH2 may prove therapeutic in diseases in which aberrant vascularization plays a role.
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Registered trials
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