MiR-494-3p aggravates pirarubicin-induced cardiomyocyte injury by regulating MDM4/p53 signaling pathway

Pirarubicin (THP) is a widely used antitumor drug in clinical practice, but its cardiotoxicity limits its use. There is an urgent need to find drugs to alleviate the cardiotoxicity of THP. This study aimed to investigate the effect and mechanism of miR-494-3p on THP-induced cardiomyocytes. THP induc...

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Bibliographic Details
Published in:Environmental toxicology 2023-10, Vol.38 (10), p.2499-2508
Main Authors: Huang, Peng, Zhang, Yibing, Wang, Fengjun, Qin, Meng, Ma, Jiulong, Ji, Jiahua, Wei, Dexian, Ren, Liqun
Format: Article
Language:English
Subjects:
Antitumour agents
Apoptosis
Cardiomyocytes
Cardiotoxicity
Cardiovascular diseases
Cell viability
Damage
Detection
Drug development
Flow cytometry
Membrane potential
p53 Protein
Signal transduction
Therapeutic targets
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Summary:Pirarubicin (THP) is a widely used antitumor drug in clinical practice, but its cardiotoxicity limits its use. There is an urgent need to find drugs to alleviate the cardiotoxicity of THP. This study aimed to investigate the effect and mechanism of miR-494-3p on THP-induced cardiomyocytes. THP induced immortalized mouse cardiomyocytes HL-1, silenced or overexpressed miR-494-3p. The effects of miR-494-3p on HL-1 contained in THP were investigated by CCK8, flow cytometry, ROS detection, JC-1 mitochondrial membrane potential detection, TUNEL cell apoptosis detection, RT-qPCR, and Western blot. miR-494-3p could reduce cell viability, increase oxidative damage, and promote cell apoptosis; at the same time, it inhibited the expression of MDM4, promoted the activation of p53, and promoted the expression of apoptosis-related proteins. MiR-494-3p inhibitors have the opposite effect. miR-494-3p can aggravate THP damage to HL-1, which may be achieved by downregulating MDM4 and promoting p53. miR-494-3p is one of the important miRNAs in THP-induced cardiotoxicity, which provides theoretical support for its possible use as a therapeutic target for THP-induced cardiovascular disease.
ISSN:1520-4081
1522-7278
DOI:10.1002/tox.23888