环状RNA在阿霉素心脏毒性中的生物学作用

The Biological Role of Circular RNA in Doxorubicin-Induced Cardiotoxicity

环状RNA(circular RNA,circRNA)是一类具有环状结构的非编码RNA分子,主要是由线性前体mRNA通过反向剪接机制产生的内源性转录物。CircRNA可以通过调节心肌细胞的增殖、迁移、分化、衰老以及凋亡等多种病理生理过程来参与心房颤动、动脉粥样硬化、心肌梗死、心力衰竭、扩张性心肌病和肥厚性心肌病等多种心血管疾病。阿霉素是一种用于抗癌治疗的常用药物,但其心脏毒性极大地限制了其临床应用。多项研究发现,circRNA与阿霉素心脏毒性之间存在密切联系,不仅能通过作为竞争性内源RNA及与蛋白质相互作用等分子机制参与阿霉素心脏毒性,还可能通过参与氧化应激、细胞凋亡、细胞焦亡、细胞自噬和铁死亡等多种细胞生物学过程来影响阿霉素心脏毒性。该文通过描述circRNA的形成过程及生物学功能,总结其在阿霉素心脏毒性中的生物学作用,旨在为阿霉素心脏毒性的治疗提供新的研究基础和理论支持。

circRNAs(circular RNAs)are a class of non-coding RNA molecules characterized by their covalent circular structure,arising from linear precursor mRNAs via a back-splicing mechanism.These endogenous transcripts have been implicated in the regulation of various pathophysiological processes in cardiomyocytes,such as proliferation,migration,differentiation,senescence,and apoptosis,playing significant roles in cardiovascular diseases including atrial fibrillation,atherosclerosis,myocardial infarction,heart failure,hypertrophic cardiomyopathy,and dilated cardiomyopathy.Doxorubicin,a chemotherapy agent widely used in cancer treatment,is notably limited in clinical application due to its cardiotoxicity.Numerous studies suggest a profound association between circRNAs and doxorubicin-induced cardiotoxicity.They participate not only through molecular mechanisms like acting as competitive endogenous RNAs and interacting with proteins but also by engaging in cellular biological processes including oxidative stress,apoptosis,pyroptosis,autophagy,and ferroptosis.This paper provides a detailed account of the formation and biological functions of circRNAs,summarizing their biological roles in doxorubicin-induced cardiotoxicity,thereby offering a novel research foundation and theoretical support for the treatment of doxorubicininduced cardiotoxicity.