{"title":"Targeting miR-144-5p/ACSM1 Axis Alleviates Doxorubicin-Induced Heart Failure by Inhibiting Lipid Peroxidation.","authors":"Guo-Ying Kao, Yi Xu, Ying Zhang, Gang Xu","doi":"10.1007/s11596-025-00053-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study investigates the role of miR-144-5p in doxorubicin (DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.</p><p><strong>Methods: </strong>Bioinformatics analysis was performed using the gene expression omnibus dataset GSE136547 to identify differentially expressed miRNAs in heart failure. DOX-induced in vitro and in vivo heart failure models were used to study the effects of miR-144-5p on cardiomyocyte viability, apoptosis, and lipid peroxidation. The targeting relationship between miR-144-5p and ACSM1 was verified using dual-luciferase reporter assays. Cardiac function was assessed by echocardiography, and biochemical markers of heart failure were measured using ELISA. The GO and KEGG enrichment analyses of ACSM1 were performed via the bioinformatic tools GeneMANIA and STRING.</p><p><strong>Results: </strong>miR-144-5p was significantly upregulated in DOX-treated cardiomyocytes and mouse hearts. Inhibition of miR-144-5p attenuated DOX-induced cardiomyocyte apoptosis, lipid peroxidation, and cardiac dysfunction. ACSM1 was identified as a direct target of miR-144-5p, and its expression was downregulated by DOX. Silencing ACSM1 abolished the protective effects of the miR-144-5p inhibitor on the viability, apoptosis, and lipid peroxidation of cardiomyocytes. Furthermore, miR-144-5p inhibition improved cardiac function in DOX-treated mice, as evidenced by reduced left ventricular dysfunction and decreased levels of heart failure markers (BNP, LDH, Ang II, and ALD).</p><p><strong>Conclusions: </strong>Our findings demonstrate that inhibiting miR-144-5p alleviates DOX-induced heart failure by targeting ACSM1 and suppressing lipid peroxidation. The miR-144-5p/ACSM1 axis may represent a novel therapeutic target for heart failure. Future studies should focus on further elucidating the mechanisms underlying this axis and exploring its potential clinical applications.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Medical Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11596-025-00053-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: This study investigates the role of miR-144-5p in doxorubicin (DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.
Methods: Bioinformatics analysis was performed using the gene expression omnibus dataset GSE136547 to identify differentially expressed miRNAs in heart failure. DOX-induced in vitro and in vivo heart failure models were used to study the effects of miR-144-5p on cardiomyocyte viability, apoptosis, and lipid peroxidation. The targeting relationship between miR-144-5p and ACSM1 was verified using dual-luciferase reporter assays. Cardiac function was assessed by echocardiography, and biochemical markers of heart failure were measured using ELISA. The GO and KEGG enrichment analyses of ACSM1 were performed via the bioinformatic tools GeneMANIA and STRING.
Results: miR-144-5p was significantly upregulated in DOX-treated cardiomyocytes and mouse hearts. Inhibition of miR-144-5p attenuated DOX-induced cardiomyocyte apoptosis, lipid peroxidation, and cardiac dysfunction. ACSM1 was identified as a direct target of miR-144-5p, and its expression was downregulated by DOX. Silencing ACSM1 abolished the protective effects of the miR-144-5p inhibitor on the viability, apoptosis, and lipid peroxidation of cardiomyocytes. Furthermore, miR-144-5p inhibition improved cardiac function in DOX-treated mice, as evidenced by reduced left ventricular dysfunction and decreased levels of heart failure markers (BNP, LDH, Ang II, and ALD).
Conclusions: Our findings demonstrate that inhibiting miR-144-5p alleviates DOX-induced heart failure by targeting ACSM1 and suppressing lipid peroxidation. The miR-144-5p/ACSM1 axis may represent a novel therapeutic target for heart failure. Future studies should focus on further elucidating the mechanisms underlying this axis and exploring its potential clinical applications.
期刊介绍:
Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.