AUTHOR=Mao Hongyun , Hu Jing , Yu Chenshuo , Xie Sicong , Chang Cheng , Peng Juanjuan , Zhang Yang 

TITLE=MicroRNAs in anthracycline cardiotoxicity: biomarkers, mechanisms, and therapeutic advances

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1614878

DOI=10.3389/fcvm.2025.1614878

ISSN=2297-055X

ABSTRACT=BackgroundAnthracycline-based chemotherapy is a highly effective treatment for numerous cancers, yet its clinical use is severely limited by cumulative, dose-dependent cardiotoxicity. MicroRNAs (miRNAs), as key post-transcriptional regulators of gene expression, play a pivotal role in the pathophysiology of cardiovascular disease, but their specific functions in anthracycline-induced cardiotoxicity (AIC) require systematic elucidation.PurposeThis review aims to systematically summarize current research on the key miRNAs, their molecular targets, and associated signaling pathways that regulate AIC, while also exploring their potential as biomarkers for early diagnosis and as therapeutic targets for intervention.MethodsA comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases for relevant studies published up to April 2025. Search terms included combinations of “microRNA,” “anthracycline,” “doxorubicin,” “cardiotoxicity,” and “cardiomyopathy.”ResultsA complex network of miRNAs is involved in the regulation of AIC. Pro-toxic miRNAs, such as miR-34a and miR-146a, exacerbate cardiomyocyte apoptosis and oxidative stress by targeting Sirtuin 1 (SIRT1) and anti-apoptotic proteins. In contrast, cardioprotective miRNAs, such as miR-21 and miR-133a, mitigate cardiac injury by inhibiting fibrosis and apoptosis pathways. This network dynamically influences the onset and progression of AIC, affecting key processes including oxidative stress, autophagy, fibrosis, and apoptosis.ConclusionMiRNAs play a dual role in the pathomechanisms of AIC, acting as both pathogenic factors and protective agents. A deeper understanding of this regulatory network provides a solid theoretical foundation for developing novel miRNA-based diagnostic biomarkers and intervention strategies to manage AIC. Future research should focus on validating clinical biomarker panels and optimizing targeted delivery systems.