Roy Sounak Ghosh
Department of Internal Medicine - Nephrology, Yale School of Medicine, New Haven, CT USA.
Nucleus (Calcutta). 2021;64(3):317-329. doi: 10.1007/s13237-021-00378-9. Epub 2021 Oct 16.
Autophagy is a homeostatic process designed to eliminate dysfunctional and aging organelles and misfolded proteins through a well-concerted pathway, starting with forming a double-membrane vesicle and culminating in the lysosomal degradation of the cargo enclosed inside the mature vesicle. As a vital sentry of cellular health, autophagy is regulated in every human disease condition and is an essential target for non-coding RNAs like microRNAs (miRNAs). miRNAs are short oligonucleotides that specifically bind to the 3'-untranslated region (UTR) of target mRNAs, thus leading to mRNA silencing, degradation, or translation blockage. This review summarizes the recent findings regarding the regulation of autophagy and autophagy-related genes by different miRNAs in various pathological conditions, including cancer, kidney and liver disorders, neurodegeneration, cardiovascular disorders, infectious diseases, aging-related conditions, and inflammation-related diseases. As miRNAs are being identified as prime regulators of autophagy in human disease, pharmacological molecules and traditional medicines targeting these miRNAs are also being tested in disease models, thus initiating a new series of therapeutic interventions targeting autophagy.
自噬是一种稳态过程,旨在通过一条协调良好的途径清除功能失调和老化的细胞器以及错误折叠的蛋白质,该过程始于形成双膜囊泡,并最终导致成熟囊泡内包裹的货物在溶酶体中降解。作为细胞健康的重要守护者,自噬在每种人类疾病状态下都受到调控,并且是非编码RNA(如微小RNA,miRNA)的重要作用靶点。miRNA是短寡核苷酸,可特异性结合靶mRNA的3'非翻译区(UTR),从而导致mRNA沉默、降解或翻译受阻。本综述总结了近期关于不同miRNA在各种病理状况下对自噬及自噬相关基因调控的研究结果,这些病理状况包括癌症、肾脏和肝脏疾病、神经退行性变、心血管疾病、传染病、衰老相关病症以及炎症相关疾病。由于miRNA被确定为人类疾病中自噬的主要调节因子,针对这些miRNA的药理分子和传统药物也正在疾病模型中进行测试,从而开启了一系列针对自噬的新治疗干预措施。