ArticleFrontiers in genetics2018
miR-499-5p Attenuates Mitochondrial Fission and Cell Apoptosis via p21 in Doxorubicin Cardiotoxicity.
Article in Frontiers in genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- miRNA Dysregulation in Cardiovascular Diseases: Current Opinion and Future Perspectives.International journal of molecular sciences · 2023Pooled it
- MicroRNAs in obesity, sarcopenia, and commonalities for sarcopenic obesity: a systematic review.Journal of cachexia, sarcopenia and muscle · 2022Pooled it
- MicroRNAs and Alarmins in Cardio-Oncology: Biomarkers and Therapeutic Implications in Skin and Breast Cancer.International journal of molecular sciences · 2026Review
- Nutritional Prevention of Oxidative Stress-Induced Cardiotoxicity in Pediatric Cardio-Oncology: Molecular Mechanisms and Translational Perspectives-A Narrative Review.International journal of molecular sciences · 2026Review
- MiRNA Regulations in Cardiotoxicity Induced by Oncologic Therapies and Possible Immune Response.Current medicinal chemistry · 2026Review
- The Role of miRNAs in Chemotherapy-Induced Cardiotoxicity.Biomedicines · 2025Review
- Non-Coding RNAs in the Regulation of Doxorubicin-Induced Cardiotoxicity.Biomolecules · 2025Review
- The role and mechanism of epigenetics in anticancer drug-induced cardiotoxicity.Basic research in cardiology · 2025Review
- The Role of MicroRNAs in the Pathogenesis of Doxorubicin-Induced Vascular Remodeling.International journal of molecular sciences · 2024Review
- MPV17 Prevents Myocardial Ferroptosis and Ischemic Cardiac Injury through Maintaining SLC25A10-Mediated Mitochondrial Glutathione Import.International journal of molecular sciences · 2024Article
- A Consolidated Understanding of the Contribution of Redox Dysregulation in the Development of Hearing Impairment.Antioxidants (Basel, Switzerland) · 2024Review
- Circulating MicroRNA as Biomarkers of Anthracycline-Induced Cardiotoxicity:JACC. CardioOncology · 2024Review
- A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging.npj aging · 2024Review
- Effect of vitamin D on cardiac hypertrophy in D-galactose-induced aging model through cardiac mitophagy.Molecular biology reports · 2023Article
- Non-coding RNAs regulating mitochondrial function in cardiovascular diseases.Journal of molecular medicine (Berlin, Germany) · 2023Review
- New Insight into Mechanisms of Cardiovascular Diseases: An Integrative Analysis Approach to Identify TheranoMiRNAs.International journal of molecular sciences · 2023Article
- Review
- Trophoblast Stem-Cell-Derived Exosomes Alleviate Cardiotoxicity of Doxorubicin via Improving Mfn2-Mediated Mitochondrial Fusion.Cardiovascular toxicology · 2023Article
- Review
- Long noncoding RNA NONMMUT015745 inhibits doxorubicin-mediated cardiomyocyte apoptosis by regulating Rab2A-p53 axis.Cell death discovery · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Doxorubicin (DOX) is a broad-spectrum anti-tumor drug, but its cardiotoxicity limits its clinical application. A better understanding of the molecular mechanisms underlying DOX cardiotoxicity will benefit clinical practice and remedy heart failure. Our present study observed that DOX caused cardiomyocyte (H9c2) apoptosis via the induction of abnormal mitochondrial fission. Notably, the expression levels of p21 increased in DOX-treated cardiomyocytes, and the silencing of p21 using siRNA greatly attenuated mitochondrial fission and apoptosis in cardiomyocytes. We also found that miR-499-5p could directly target p21 and attenuated DOX-induced mitochondrial fission and apoptosis. The role of the miR-499-5p-p21 axis in the prevention of DOX cardiotoxicity was also validated in the mice model. DOX treatment induced an upregulation of p21, which induced subsequent abnormal mitochondrial fission and myocardial apoptosis in mouse heart. Adenovirus-harboring miR-499-5p-overexpressing mice exhibited significantly reduced p21 expression, mitochondrial fission and myocardial apoptosis in hearts following DOX administration. The miR-499-5p-overexpressing mice also exhibited improved cardiomyocyte hypertrophy and cardiac function after DOX treatment. However, miR-499-5p was not involved in the DOX-induced apoptosis of cancer cells. Taken together, these findings reveal an emerging role of p21 in the regulation of mitochondrial fission program. miR-499-5p attenuated mitochondrial fission and DOX cardiotoxicity via the targeting of p21. These results provide new evidence for the miR-499-5p-p21 axis in the attenuation of DOX cardiotoxicity. The development of new therapeutic strategies based on the miR-499-5p-p21 axis is a promising path to overcome DOX cardiotoxicity as a chemotherapy for cancer treatment.
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Registered trials
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