Mao Hongyun, Hu Jing, Yu Chenshuo, Xie Sicong, Chang Cheng, Peng Juanjuan, Zhang Yang
Department of Rehabilitation Medicine, School of Acupuncture-Moxibustion and Tuina and School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, China.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Front Cardiovasc Med. 2025 Aug 22;12:1614878. doi: 10.3389/fcvm.2025.1614878. eCollection 2025.
Anthracycline-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.
This 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.
A 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."
A 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.
MiRNAs 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.
基于蒽环类药物的化疗是多种癌症的高效治疗方法，但其临床应用因累积性、剂量依赖性心脏毒性而受到严重限制。微小RNA（miRNA）作为基因表达的关键转录后调节因子，在心血管疾病的病理生理学中起关键作用，但其在蒽环类药物诱导的心脏毒性（AIC）中的具体功能需要系统阐明。
本综述旨在系统总结当前关于调节AIC的关键miRNA、其分子靶点及相关信号通路的研究，同时探讨它们作为早期诊断生物标志物和干预治疗靶点的潜力。
在PubMed、Web of Science和Scopus数据库中进行全面的文献检索，以查找截至2025年4月发表的相关研究。检索词包括“微小RNA”“蒽环类药物”“阿霉素”“心脏毒性”和“心肌病”的组合。
一个复杂的miRNA网络参与AIC的调节。促毒性miRNA，如miR-34a和miR-146a，通过靶向沉默调节蛋白1（SIRT1）和抗凋亡蛋白加剧心肌细胞凋亡和氧化应激。相反，心脏保护miRNA，如miR-21和miR-133a，通过抑制纤维化和凋亡途径减轻心脏损伤。该网络动态影响AIC的发生和发展，影响包括氧化应激、自噬、纤维化和凋亡在内的关键过程。
miRNA在AIC的发病机制中起双重作用，既是致病因素又是保护因子。对这一调节网络的深入理解为开发基于miRNA的新型诊断生物标志物和管理AIC的干预策略提供了坚实的理论基础。未来的研究应专注于验证临床生物标志物组合和优化靶向递送系统。
