title: MicroRNA-125a-5p Contributes to Hepatic Stellate Cell Activation through Targeting FIH1.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our findings shed new light on miRNAs as a promising therapeutic target in liver fibrosis.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Changshui
authors.initials: C
authors.lastname: Li
authors.forename: Honggang
authors.initials: H
authors.lastname: Qi
authors.forename: Peihong
authors.initials: P
authors.lastname: Dong
authors.forename: Jianjian
authors.initials: J
authors.lastname: Zheng
authors.forename: Fujun
authors.initials: F
authors.lastname: Yu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D049109:Cell Proliferation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D057809:HEK293 Cells; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009841:Oligonucleotides / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016415:Sequence Alignment; D015854:Up-Regulation
chemical_list: D000199:Actins; D024042:Collagen Type I; D035683:MicroRNAs; D009841:Oligonucleotides; D034741:RNA, Small Interfering; C544013:alpha-smooth muscle actin, mouse; D002251:Carbon Tetrachloride; D006899:Mixed Function Oxygenases; C551240:factor inhibiting hypoxia-inducible factor 1, mouse