Targeting miR-144-5p/ACSM1 Axis Alleviates Doxorubicin-Induced Heart Failure by Inhibiting Lipid Peroxidation.

IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Guo-Ying Kao, Yi Xu, Ying Zhang, Gang Xu
{"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.

靶向miR-144-5p/ACSM1轴通过抑制脂质过氧化减轻阿霉素诱导的心力衰竭
目的:本研究探讨miR-144-5p在多柔比星(DOX)诱导心力衰竭中的作用,并通过靶向ACSM1抑制脂质过氧化,探讨其潜在机制。方法:利用基因表达综合数据集GSE136547进行生物信息学分析,鉴定心力衰竭中差异表达的mirna。采用dox诱导的体外和体内心力衰竭模型,研究miR-144-5p对心肌细胞活力、凋亡和脂质过氧化的影响。通过双荧光素酶报告基因检测验证miR-144-5p与ACSM1之间的靶向关系。超声心动图检测心功能,ELISA检测心衰生化指标。ACSM1的GO和KEGG富集分析通过生物信息学工具GeneMANIA和STRING进行。结果:在dox处理的心肌细胞和小鼠心脏中,miR-144-5p显著上调。抑制miR-144-5p可减轻dox诱导的心肌细胞凋亡、脂质过氧化和心功能障碍。ACSM1被确定为miR-144-5p的直接靶点,其表达被DOX下调。沉默ACSM1可消除miR-144-5p抑制剂对心肌细胞活力、凋亡和脂质过氧化的保护作用。此外,miR-144-5p抑制改善了dox处理小鼠的心功能,左心室功能障碍减轻,心衰标志物(BNP、LDH、Ang II和ALD)水平降低。结论:我们的研究结果表明,抑制miR-144-5p通过靶向ACSM1和抑制脂质过氧化来减轻dox诱导的心力衰竭。miR-144-5p/ACSM1轴可能代表心力衰竭的新治疗靶点。未来的研究应集中于进一步阐明这一轴的机制并探索其潜在的临床应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Current Medical Science
Current Medical Science Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.70
自引率
0.00%
发文量
126
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信