Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
Gut. 2021 Apr;70(4):784-795. doi: 10.1136/gutjnl-2020-322526. Epub 2020 Oct 30.
MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression by binding to specific mRNA targets and promoting their degradation and/or translational inhibition. miRNAs regulate both physiological and pathological liver functions. Altered expression of miRNAs is associated with liver metabolism dysregulation, liver injury, liver fibrosis and tumour development, making miRNAs attractive therapeutic strategies for the diagnosis and treatment of liver diseases. Here, we review recent advances regarding the regulation and function of miRNAs in liver diseases with a major focus on miRNAs that are specifically expressed or enriched in hepatocytes (miR-122, miR-194/192), neutrophils (miR-223), hepatic stellate cells (miR-29), immune cells (miR-155) and in circulation (miR-21). The functions and target genes of these miRNAs are emphasised in alcohol-associated liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, viral hepatitis and hepatocellular carcinoma, as well liver fibrosis and liver failure. We touch on the roles of miRNAs in intercellular communication between hepatocytes and other types of cells via extracellular vesicles in the pathogenesis of liver diseases. We provide perspective on the application of miRNAs as biomarkers for early diagnosis, prognosis and assessment of liver diseases and discuss the challenges in miRNA-based therapy for liver diseases. Further investigation of miRNAs in the liver will help us better understand the pathogeneses of liver diseases and may identify biomarkers and therapeutic targets for liver diseases in the future.
微小 RNA(miRNAs)是一类小型非编码 RNA,通过与特定的 mRNA 靶标结合,促进其降解和/或翻译抑制,从而在后转录水平上调节基因表达。miRNAs 调节肝脏的生理和病理功能。miRNAs 的表达改变与肝脏代谢失调、肝损伤、肝纤维化和肿瘤发展有关,这使得 miRNAs 成为诊断和治疗肝脏疾病的有吸引力的治疗策略。在这里,我们综述了 miRNA 在肝脏疾病中的调控和功能的最新进展,重点关注在肝细胞中特异性表达或富集的 miRNA(miR-122、miR-194/192)、中性粒细胞(miR-223)、肝星状细胞(miR-29)、免疫细胞(miR-155)和循环中的 miRNA(miR-21)。这些 miRNA 的功能和靶基因在酒精相关性肝病、非酒精性脂肪性肝病、药物性肝损伤、病毒性肝炎和肝细胞癌,以及肝纤维化和肝功能衰竭中得到了强调。我们还探讨了 miRNA 在通过细胞外囊泡进行的肝细胞与其他类型细胞之间的细胞间通讯中的作用,在肝脏疾病的发病机制中。我们提供了 miRNA 作为早期诊断、预后和评估肝脏疾病的生物标志物的应用前景,并讨论了 miRNA 治疗肝脏疾病的挑战。对肝脏中 miRNA 的进一步研究将帮助我们更好地理解肝脏疾病的发病机制,并可能为未来的肝脏疾病确定生物标志物和治疗靶点。