细胞外囊泡中miRNA的分泌机制

Mechanism of miRNA secretion into extracellular vesicles

细胞外囊泡(extracellular vesicles,EVs)是一类在生理和病理条件下所有细胞均可分泌的双层膜囊泡。EVs可以包裹很多供体细胞来源的分子物质(蛋白质、脂类、核酸和代谢产物等),并将所携带的分子物质释放到受体细胞内,从而调节受体细胞的生物学功能。在EVs携带的分子物质中,microRNA(miRNA)是被广泛研究的一类包含物。EVs中miRNA(EV-miRNAs)作为信号分子介导细胞间通讯,调控受体细胞的基因表达,在诸多生理和病理过程中发挥着重要的作用。由于EVs的miRNA表达谱与亲本细胞的miRNA表达谱不同,表明EV-miRNAs并非随机释放而是选择性地被包装到EVs中。该综述主要对EVs生成、转运以及EVs中miRNA的分泌机制进行介绍,这些机制包括RNA结合蛋白、miRNA序列特征、miRNA介导的沉默复合体、参与EVs生物生成的膜蛋白等。此外,某些生理病理状态也影响EV-miRNAs分泌,揭示了选择性分泌机制在疾病进程中的潜在作用。同时,本综述讨论了EV-miRNAs作为生物标志物在疾病诊疗中的应用价值。

Extracellular vesicles(EVs)are bilayer vesicles secreted by all cells under physiological and pathological conditions.EVs can encapsulate many molecular substances(proteins,lipids,nucleic acids,metabolites,etc.)from donor cells,and release the carried molecular substances into the recipient cells,thereby regulating the biological function of the recipient cells.Among the molecular substances carried by EVs,microRNA(miRNA)are a class of inclusions that have been widely studied.As signaling molecules,miRNA in EVs(EV-miRNAs)can mediate intercellular communication,regulate gene expression of receptor cells,and play an important role in many physiological and pathological processes.Since the miRNA expression profile of EVs is different from that of parent cells,EV-miRNAs are not released randomly but selectively packaged into EVs.This review mainly introduces the formation,transport of EVs and the mechanism of miRNA secretion into EVs.These mechanisms include RNA-binding proteins,miRNA sequence signatures,miRNA induced silencing complexes,and membrane proteins involved in EVs biogenesis.In addition,certain physiological and pathological states also affect EV-miRNAs secretion,revealing the potential role of selective secretion mechanisms in disease.At the same time,this review discusses the application value of EV-miRNAs as biomarkers in disease diagnosis and treatment.