Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Int J Mol Sci. 2018 Jan 16;19(1):261. doi: 10.3390/ijms19010261.
Both acute and chronic liver toxicity represents a major global health burden and an important cause of morbidity and lethality worldwide. Despite epochal progress in the treatment of hepatitis C virus infections, pharmacological treatment strategies for most liver diseases are still limited and new targets for prevention or treatment of liver disease are urgently needed. MicroRNAs (miRNAs) represent a new class of highly conserved small non-coding RNAs that are involved in the regulation of gene expression by targeting whole networks of so called "targets". Previous studies have shown that the expression of miRNAs is specifically altered in almost all acute and chronic liver diseases. In this context, it was shown that miRNA can exert causal roles, being pro- or anti-inflammatory, as well as pro- or antifibrotic mediators or being oncogenes as well as tumor suppressor genes. Recent data suggested a potential therapeutic use of miRNAs by targeting different steps in the hepatic pathophysiology. Here, we review the function of miRNAs in the context of acute and chronic liver diseases. Furthermore, we highlight the potential role of circulating microRNAs in diagnosis of liver diseases and discuss the major challenges and drawbacks that currently prevent the use of miRNAs in clinical routine.
急性和慢性肝毒性均代表着全球重大的健康负担,也是世界范围内发病率和死亡率的重要原因。尽管丙型肝炎病毒感染的治疗取得了划时代的进展,但大多数肝脏疾病的药物治疗策略仍然有限,迫切需要新的预防或治疗肝脏疾病的靶点。微小 RNA(miRNA)是一类新的高度保守的小非编码 RNA,通过靶向所谓的“靶标”的整个网络来参与基因表达的调控。先前的研究表明,miRNA 的表达在几乎所有急性和慢性肝病中都发生了特异性改变。在这种情况下,已经证明 miRNA 可以发挥因果作用,作为促炎或抗炎、促纤维化或抗纤维化的介质,或者作为癌基因和抑癌基因。最近的数据表明,通过靶向肝病理生理学的不同步骤,miRNA 具有潜在的治疗用途。在这里,我们回顾了 miRNA 在急性和慢性肝病中的作用。此外,我们强调了循环 microRNAs 在诊断肝脏疾病中的潜在作用,并讨论了目前阻止 miRNA 在临床常规中使用的主要挑战和缺陷。