ArticlePloS one2013
MiR-499 regulates cell proliferation and apoptosis during late-stage cardiac differentiation via Sox6 and cyclin D1.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Pooled it
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- Strong Association Between MiRNA Gene Variants and Type 2 Diabetes Mellitus in a Caucasian Population.International journal of molecular sciences · 2025Article
- miRNA genetic variations associated with the predisposition of oral squamous cell carcinoma in central Indian population.Non-coding RNA research · 2024Article
- The Potential Contribution of MyomiRs miR-133a-3p, -133b, and -206 Dysregulation in Cardiovascular Disease Risk.International journal of molecular sciences · 2024Article
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- Targeting cardiomyocyte cell cycle regulation in heart failure.Basic research in cardiology · 2024Review
- MicroRNAs and Cardiovascular Disease Risk.Current cardiology reports · 2024Review
- Propranolol inhibits EMT and metastasis in breast cancer through miR-499-5p-mediated Sox6.Journal of cancer research and clinical oncology · 2024Article
- miRNAs Epigenetic Tuning of Wall Remodeling in the Early Phase after Myocardial Infarction: A Novel Epidrug Approach.International journal of molecular sciences · 2023Review
- Review
- Cardiac microRNAs: diagnostic and therapeutic potential.Archives of medical science : AMS · 2023Article
- Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation.Open medicine (Warsaw, Poland) · 2023Article
- Association between miR-146a rs2910164, miR-196a2 rs11614913, and miR-499 rs3746444 polymorphisms and the risk of esophageal carcinoma: A case-control study.Cancer medicine · 2022Article
- Upregulation ofInternational journal of molecular sciences · 2022Article
- Extracellular vesicles as mediators and markers of acute organ injury: current concepts.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2022Review
- Sox6, A Potential Target for MicroRNAs in Cardiometabolic Disease.Current hypertension reports · 2022Review
- Cardioprotective effect of extracellular vesicles derived from ticagrelor-pretreated cardiomyocyte on hyperglycemic cardiomyocytes through alleviation of oxidative and endoplasmic reticulum stress.Scientific reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMiR-499 is a cardiac-abundant miRNA. However, the biological functions of miR-499 in differentiated cardiomyocytes or in the cardiomyocyte differentiation process is not very clear. Sox6 is believed to be one of its targets, and is also believed to play a role in cardiac differentiation. Therefore, our aim was to investigate the association between Sox6 and miR-499 during cardiac differentiation. METHODOLOGY/PRINCIPAL
findingsUsing a well-established in vitro cardiomyocyte differentiation system, mouse P19CL6 cells, we found that miR-499 was highly expressed in the late stage of cardiac differentiation. In cells stably transfected with miR-499 (P-499 cells), it was found that miR-499 could promote the differentiation into cardiomyocytes at the early stage of cardiac differentiation. Notably, cell viability assay, EdU incorporation assay, and cell cycle profile analysis all showed that the P-499 cells displayed the distinctive feature of hyperplastic growth. Further investigation confirmed that miR-499 could promote neonatal rat cardiomyocyte proliferation. MiR-499 knock-down enhanced apoptosis in the late differentiation stage in P19CL6 cells, but overexpression of miR-499 resulted in a decrease in the apoptosis rate. Sox6 was identified as a direct target of miR-499 and its expression was detected from day 8 or day 10 of cardiac differentiation of P19CL6 cells. Sox6 played a role in cell viability, inhibited cell proliferation and promoted cell apoptosis in P19CL6 cells and cardiomyocytes. The overexpression of Sox6 could reverse the proliferation and anti-apoptosis effects of miR-499. It was also found that miR-499 might exert its function by regulating cyclin D1 via its influence on Sox6. CONCLUSIONS/SIGNIFICANCE: miR-499 probably regulates the proliferation and apoptosis of P19CL6 cells in the late stage of cardiac differentiation via its effects on Sox6 and cyclin D1.
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