MiR-122 in hepatic function and liver diseases

As the most abundant liver-specific microRNA,mi-croRNA-122(miR-122)is involved in various physio-logical processes in hepatic function as well as in liver pathology.There is now compelling evidence that miR-122,as a regulator of gene networks and pathways in hepatocytes,plays a central role in diverse aspects of hepatic function and in the progress of liver diseases.This liver-enriched transcription factors-regulated miRNA promotes differentiation of hepatocytes and regulates lipid metabolism.With regard to liver diseases,miR-122 was shown to stimulate hepatitis C virus(HCV)replication through a unique and unusual interaction with two binding sites in the 5′-UTR of HCV genome to mediate the stability of the viral RNA,whereas inhibit the expression and replication of hepatitis B virus(HBV)by a miR-122-cylin G1/p53-HBV enhancer regulatory pathway.In addition,miR-122 acts as a suppressor of cell prolif-eration and malignant transformation of hepatocytes with remarkable tumor inhibition activity.Notably,a clinical trial targeting miR-122 with the anti-miR-122 oli-gonucleotides miravirsen,the first miRNA targeted drug,has been initiated for treatment of HCV infection.With further understanding of the comprehensive roles of miR-122 in hepatic functions and the mechanisms in-volved in miR-122 down-regulation in chronic hepatitis or hepatocellular carcinoma,miR-122 appears to be a promising candidate for effective therapeutic ap-proaches against tumor and infectious diseases.