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Updated: Nov 16, 2025
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
MiR-200a-3p Aggravates DOX-Induced Cardiotoxicity by Targeting PEG3 Through SIRT1/NF-κB Signal Pathway
Qinghua Fu1, Hongwei Pan2, Yi Tang2
1Department of Cardiovasology, Hunan Provincial People's Hospital, Changsha, Hunan, 410000, People's Republic of China. 56071317@qq.com.
Abstract:
Doxorubicin (DOX) is a widely used cytotoxic drug whose application is limited by its severe side effects. Little was known regarding how to offset its side effects. Therefore this study aims to explore the role of miR-200a-3p in DOX-induced cardiotoxicity and its possible mechanism. DOX-induced myocardial injury rat models were established, which were then injected with miR-200a-3p inhibitor (miR-200a-3p suppression) to observe the effects of miR-200a-3p on cell proliferation, and apoptosis. Heart function and weights of rat models were also measured. Cardiomyocytes were induced by DOX, in which PEG3 knockdown or corresponding plasmids were transfected to assess the possible effect of PEG3 on cell activity. Dual luciferase reporter assay was applied to verify the binding of PEG3 with miR-200a-3p. Elevated levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and left ventricular end-diastolic pressure (LVEDP), as well as suppressed left ventricular systolic pressure (LVSP) and ± dp/dt max were showed in myocardial injury rat models. DOX induced myocardial injury and increased miR-200a-3p expression levels. miR-200a-3p inhibitor could partially attenuate DOX-induced cardiotoxicity in rat models, while PEG3 could regulate myocardial injury in DOX-treated cell models. miR-200a-3p, by targeting PEG3 through SIRT1/NF-κB signal pathway, regulated cell proliferation, inflammation and apoptosis of myocardiocytes. The results in current study demonstrated that miR-200a-3p regulates cell proliferation and apoptosis of cardiomyocytes by targeting PEG3 through SIRT1/NF-κB signal pathway. This result may provide a potential clue for the treatment of DOX-induced cardiotoxicity.
Insights
MicroRNA-200a-3p (miR-200a-3p) can mitigate doxorubicin-induced cardiotoxicity by targeting PEG3. This study reveals miR-200a-3p
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiology
Background:
- Doxorubicin (DOX) is a vital chemotherapy agent with dose-limiting cardiotoxicity.
- Mechanisms to counteract DOX-induced cardiotoxicity remain largely unexplored.
- MicroRNAs (miRNAs) are emerging as key regulators in cellular processes and disease.
Purpose of the Study:
- To investigate the role of miR-200a-3p in doxorubicin-induced cardiotoxicity.
- To elucidate the underlying molecular mechanisms involving PEG3 and the SIRT1/NF-κB pathway.
- To explore miR-200a-3p as a potential therapeutic target for mitigating DOX side effects.
Main Methods:
- Establishment of DOX-induced myocardial injury rat models.
- Administration of miR-200a-3p inhibitors and assessment of cardiac function and biomarkers (LDH, CK-MB, LVEDP, LVSP).
- In vitro studies using DOX-treated cardiomyocytes with PEG3 knockdown/transfection and dual luciferase reporter assays to confirm target interaction.
Main Results:
- DOX treatment significantly impaired heart function and increased myocardial injury markers in rats.
- miR-200a-3p expression was upregulated in DOX-induced cardiotoxicity.
- Inhibition of miR-200a-3p partially attenuated DOX-induced cardiotoxicity, while PEG3 modulation affected cardiomyocyte viability in vitro.
- miR-200a-3p directly targets PEG3, influencing the SIRT1/NF-κB pathway to regulate cardiomyocyte proliferation, apoptosis, and inflammation.
Conclusions:
- miR-200a-3p plays a protective role against DOX-induced cardiotoxicity.
- The mechanism involves miR-200a-3p targeting PEG3, thereby modulating the SIRT1/NF-κB signaling pathway.
- miR-200a-3p represents a promising therapeutic strategy for managing chemotherapy-induced heart damage.
