MiR-122 in hepatic function and liver diseases

被引:165
作者
Hu, Jun [1 ]
Xu, Yaxing [1 ]
Hao, Junli [1 ]
Wang, Saifeng [1 ]
Li, Changfei [1 ]
Meng, Songdong [1 ]
机构
[1] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-122; liver development; lipid metabolism; hepatitis C virus (HCV); hepatitis B virus (HBV); hepatocellular carcinoma (HCC); C VIRUS-RNA; B-VIRUS; HEPATOCELLULAR-CARCINOMA; MICRORNA MIR-122; CELL-PROLIFERATION; IN-VIVO; EXPRESSION; REPLICATION; MODULATION; IDENTIFICATION;
D O I
10.1007/s13238-012-2036-3
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
As the most abundant liver-specific microRNA, microRNA-122 (miR-122) is involved in various physiological 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 proliferation and malignant transformation of hepatocytes with remarkable tumor inhibition activity. Notably, a clinical trial targeting miR-122 with the anti-miR-122 oligonucleotides 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 involved in miR-122 down-regulation in chronic hepatitis or hepatocellular carcinoma, miR-122 appears to be a promising candidate for effective therapeutic approaches against tumor and infectious diseases.
引用
收藏
页码:364 / 371
页数:8
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