铁死亡相关的环状RNA在疾病中的作用及机制

The Mechanism and Role of Ferroptosis-related Circular RNAs in Diseases

环状RNA(circular RNA,circRNA)是真核生物细胞中一类特殊的非编码RNA(non-coding RNA,ncRNA),具有高度稳定性。目前已广泛发现circRNA可作为微RNA(microRNA,miRNA)海绵参与各种疾病发生发展过程。作为近年来研究的热点,circRNA的功能和作用不断被发现和利用,其既可作为蛋白质支架使靶点结合更紧密,也可以调节疾病信号分子的转录表达,还能作为翻译模板,参与蛋白质的表达。此外,研究证实了铁死亡在疾病发展中具有重要作用,而铁死亡相关circRNA的分子机制研究也是医学研究领域的新前沿。最近研究发现,circRNA不仅能作为miRNA和蛋白质支架参与调控铁死亡,还能从转录水平调节铁死亡相关信号分子。目前,人工合成的环状RNA已被设计用于RNA疫苗,各种基因治疗技术、药物递送载体也为靶向circRNA的药物开发提供重要依据。本文阐述了circRNA的功能和作用、铁死亡调控的关键靶点及其在疾病中的作用,并且着重阐释了铁死亡相关circRNA在肿瘤、神经系统疾病及糖尿病并发症等多系统疾病中的作用机制,概述了circRNA相关的药物开发策略,为基于铁死亡相关circRNA的药物开发提供新的思路。

Circular RNA(circRNA)is a special class of non-coding RNA(ncRNA)in eukaryotic cells,which is highly stable.At present,circRNA has been widely found to be involved in the occurrence and development of various diseases as microRNA(miRNA)sponges.As a research hotspot in recent years,the function and effects of circRNA are constantly being discovered and utilized.CircRNAs can act as protein scaffolds to bind targets more tightly and regulate transcription of disease signaling molecules,as well as participate in protein expression as translation templates.A substantial body of research has established the pivotal role of ferroptosis in disease development.Iron and lipid metabolism-related targets are recognized as key components in the regulation of ferroptosis.Recent studies have revealed that circRNA not only participates in ferroptosis regulation as a miRNA and protein scaffold but also exerts control over ferroptosis-related signaling molecules at the transcriptional level.Currently,synthetic circRNA molecules have been engineered for the development of RNA vaccines.Additionally,a range of gene therapy technologies and drug delivery vectors offer a promising foundation for the development of therapeutics targeting circRNA.This paper describes the functions and effects of circRNA,its role as a key target in the regulation of ferroptosis,and its implications in various diseases.Special emphasis is placed on discussing the role of circRNA in multisystem diseases,including tumors,nervous system disorders,and diabetes-related complications.Additionally,drug development strategies related to circRNA are summarized to provide insights for the development of therapeutic drugs targeting ferroptosis.