ArticleJournal of molecular and cellular cardiology2015
miR-200c-SUMOylated KLF4 feedback loop acts as a switch in transcriptional programs that control VSMC proliferation.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Activation of developmental transcription factors using RNA technology promotes heart repair.bioRxiv : the preprint server for biology · 2026Article
- Macrophage-like smooth muscle cells in atherosclerosis.Molecular biology reports · 2025Review
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- Single-nuclei multiomics analysis identifies abnormal cardiomyocytes in a murine model of cardiac development.Nature communications · 2025Article
- Extracellular derived-exosomal micrornas in pancreatic cancer: investigating their diagnostic importance and potential targets for the prevention and treatment in pancreatic cancer.Frontiers in oncology · 2025Review
- The Role of MicroRNAs in the Pathogenesis of Doxorubicin-Induced Vascular Remodeling.International journal of molecular sciences · 2024Review
- SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling.Nature communications · 2024Article
- Proteomics Studies Suggest That Nitric Oxide Donor Furoxans Inhibit In Vitro Vascular Smooth Muscle Cell Proliferation by Nitric Oxide-Independent Mechanisms.Molecules (Basel, Switzerland) · 2023Article
- MicroRNA regulation of phenotypic transformations in vascular smooth muscle: relevance to vascular remodeling.Cellular and molecular life sciences : CMLS · 2023Review
- Noncoding RNAs in Vascular Cell Biology and Restenosis.Biology · 2022Review
- Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis.International journal of molecular sciences · 2022Review
- Discoidin Domain-Containing Receptor 2 Is Present in Human Atherosclerotic Plaques and Involved in the Expression and Activity of MMP-2.Oxidative medicine and cellular longevity · 2021Article
- Expression and Functional Analysis of lncRNAs Involved in Platelet-Derived Growth Factor-BB-Induced Proliferation of Human Aortic Smooth Muscle Cells.Frontiers in cardiovascular medicine · 2021Article
- MiRNA 3613-5p and MiRNA 3916 rescued the inhibition of cell migration in CNOT2 depleted MDA-MD-231 cells.Translational cancer research · 2020Article
- Screening and functional prediction of differentially expressed circRNAs in proliferative human aortic smooth muscle cells.Journal of cellular and molecular medicine · 2020Article
- Transcription Factors Targeted by miRNAs Regulating Smooth Muscle Cell Growth and Intimal Thickening after Vascular Injury.International journal of molecular sciences · 2019Review
- The microRNAs Regulating Vascular Smooth Muscle Cell Proliferation: A Minireview.International journal of molecular sciences · 2019Review
- Imbalance of a KLF4-miR-7 auto-regulatory feedback loop promotes prostate cancer cell growth by impairing microRNA processing.American journal of cancer research · 2018Article
- miR-29a regulates vascular neointimal hyperplasia by targeting YY1.Cell proliferation · 2017Article
- SUMOylation of KLF4 promotes IL-4 induced macrophage M2 polarization.Cell cycle (Georgetown, Tex.) · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
The regulation of vascular smooth muscle cell (VSMC) proliferation is an important issue because it has major implications for the prevention of pathological vascular conditions. Using microRNA array screen, we found the expression levels of 200 unique miRNAs in hyperplasic tissues. Among them, miR-200c expression substantially was down-regulated. The objective of this work was to assess the function of miR-200c and SUMOylated Krϋppel-like transcription factor 4 (KLF4) in the regulation of VSMC proliferation in both cultured cells and animal models of balloon injury. Under basal conditions, we found that miR-200c inhibited the expression of KLF4 and the SUMO-conjugating enzyme Ubc9. Upon PDGF-BB treatment, Ubc9 interacted with and promoted the SUMOylation of KLF4, which allowed the recruitment of transcriptional corepressors (e.g., nuclear receptor corepressor (NCoR) and HDAC2) to the miR-200c promoter. The reduction in miR-200c levels led to increased target gene expression (e.g., Ubc9 and KLF4), which further repressed miR-200c levels and accelerated VSMC proliferation. These results demonstrate that induction of a miR-200c-SUMOylated KLF4 feedback loop is a significant aspect of the PDGF-BB proliferative response in VSMCs and that targeting Ubc9 represents a novel approach for the prevention of restenosis.
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