心律失常调节的新靶点--microRNA的研究进展与应用前景

Basic research and application of microRNA——a novel target for regulating cardiac arrhythmias

转化医学是近年来提出的关于基础与临床密切结合的新概念,其目的是实现基础研究成果真正转化为临床实践。microRNA(miRNA)是新发现的基因表达调控因子,由长约21～25核苷酸的单链RNA分子构成。近年来,miRNA在心血管系统中的关键调控作用不断得以阐明,尤其是在心律失常中的调节作用,取得了令人瞩目的研究成果。一系列研究证实miRNA参与调控多种心脏电活动相关蛋白的表达,是心律失常发生和抗心律失常药物作用的潜在靶点。miRNA作为治疗靶点通过调节靶基因mRNA的稳定性或抑制翻译过程而发挥作用。在靶器官中稳定相应miRNA的表达水平可能成为疾病治疗的一个新方式。本文将从miRNA表达改变引起功能失调这一角度,采用拟miRNA技术和抗miRNA技术纠正靶蛋白的功能,为心律失常的治疗提供新的切入点。借助miRNA类似物(miRNA mimics)和胆固醇连接的miRNA反义核苷酸抑制剂(antagomirs),miRNA用于治疗多种心血管疾病有望实现,将为转化医学的实现注入新的动力。

Translational medicine is a novel concept about combination of basic research and clinical application.The aim of translational medicine is to realize the translation of basic research into clinical practice.microRNAs（miRNAs） are non-coding single-stranded RNAs with 21-25 nucleotides in length as newly discovered factors in regulating gene expression.Recently,the key regulatory role of miRNA in the cardiovascular system has been elucidated and amount of remarkable results has been achieved,particularly in the regulation of cardiac arrhythmias.A series of studies demonstrate that miRNAs are involved in the regulation of expression of a variety of proteins associated with cardiac electrical activity,and are the potential targets of occurrence of cardiac arrhythmias and anti-arrhythmic drugs.miRNAs as a therapeutic target regulate the stability of mRNAs of target genes or play an inhibitory role in the translation process.Stability of the corresponding miRNA expression levels in the target organ may be a new approach for the disease therapy.Regarding the dysfunction of miRNA,we employed miRNA re-expression strategy and anti-miRNA strategy to correct target protein function and provide a new entry for the therapy of arrhythmia.With the technology of miRNA mimics and antagomirs,miRNAs are expected to treat various cardiovascular diseases and will provide a fresh impetus to achieve transform medicine.