MicroRNA-125a-5p Contributes to Hepatic Stellate Cell Activation through Targeting FIH1

• Published in: Cellular physiology and biochemistry Vol. 38; no. 4; pp. 1544 - 1552
• Main Authors: Li, Guojun, Li, Jing, Li, Changshui, Qi, Honggang, Dong, Peihong, Zheng, Jianjian, Yu, Fujun
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01.04.2016
• Subjects: Actins - metabolism; Animals; Carbon Tetrachloride - toxicity; Cell Proliferation; Cells, Cultured; Collagen Type I - genetics; Collagen Type I - metabolism; Disease Models, Animal; Down-Regulation; FIH1; HEK293 Cells; Hepatic stellate cells; Hepatic Stellate Cells - cytology; Hepatic Stellate Cells - metabolism; Hepatocytes - cytology; Hepatocytes - metabolism; Humans; Liver Cirrhosis - etiology; Liver Cirrhosis - metabolism; Liver fibrosis; Male; Mice; Mice, Inbred C57BL; MicroRNA; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-125a-5p; Mixed Function Oxygenases - antagonists & inhibitors; Mixed Function Oxygenases - genetics; Mixed Function Oxygenases - metabolism; Oligonucleotides - metabolism; Original Paper; RNA, Small Interfering - metabolism; Sequence Alignment; Up-Regulation; MiR-125a-5p; Hepatic stellate cells; MicroRNA; Liver fibrosis; FIH1
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000443095

Background/Aims: Emerging evidence shows that microRNAs (miRNAs) play a crucial role in the regulation of activation, proliferation and apoptosis of hepatic stellate cells (HSCs). Previous studies have indicated that miR-125a-5p is correlated with hepatitis B virus replication and disease progression. However, little is known about the biological role and underlying mechanism of miR-125a-5p in liver fibrosis. Methods: We analyzed the level of miR-125a-5p in carbon tetrachloride-induced liver fibrosis and activated HSCs. We analyzed the effects of miR-125a-5p down-regulation on HSC activation and proliferation. We also analyzed the binding of miR-125a-5p to the 3′-untranslated region of factor inhibiting hypoxia-inducible factor 1 (FIH1) mRNA. Results: Up-regulation of miR-125a-5p was observed in the liver tissues of fibrotic mice and activated HSCs. Down-regulation of miR-125a-5p prevented the activation and proliferation of HSCs. FIH1, a negative modulator of hypoxia inducible factor 1, was confirmed to be a target of miR-125a-5p using the luciferase reporter assay. Further studies demonstrated that miR-125a-5p prompted the activation and proliferation of HSCs, at least in part, by down-regulating FIH1. Conclusion: Our findings shed new light on miRNAs as a promising therapeutic target in liver fibrosis.