title: Upregulated microRNA-199a-5p inhibits nuclear receptor corepressor 1 translation in mice with non‑alcoholic steatohepatitis.
abstract: Mounting evidence indicates that dysregulated microRNAs (miRNAs) are important in the etiology and pathogenesis of steatohepatitis. However, the functions of miRNAs in the pathophysiological process of non-alcoholic steatohepatitis (NASH) are poorly understood. In this study, C57BL/6J mice were fed a methionine-choline‑deficient (MCD) diet for eight weeks in order to induce hepatic steatohepatitis. Using reverse transcription polymerase chain reaction, the hepatic expression levels of miR-199a-5p, miR-122 and miR-221 in the mice were examined. Bioinformatic analysis of dysregulated miR-199a-5p was performed to predict the potential role of miR‑199a‑5p in NASH. The MCD diet was found to significantly reduce miR-122 expression levels and significantly increase miR‑199a-5p expression levels in mouse livers, compared with those of mice fed a control diet. In the bioinformatic analysis, miR‑199a‑5p was identified to be predominantly involved in transcription, protein serine/threonine kinase activity, insulin signaling, and the Wnt and mitogen‑activated protein kinase signaling pathways. The regulation of nuclear receptor corepressor 1 (NCOR1) by miR‑199a-5p was also examined by silencing and overexpressing this miRNA in LX-2 cells. The data revealed that NCOR1 protein levels were significantly reduced and enhanced by miR-199a-5p mimic and inhibitor, respectively. These findings suggest a key role for miR-199a-5p in the progression of NASH through inhibition of NCOR1 translation, and provide novel insights into NASH pathogenesis.
authors.affiliation: Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Binggui
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Rongqi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of General Surgery, Hebei Provincial Geriatric Hospital, Shijiazhuang, Hebei 050031, P.R. China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Niu
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Shunjiang
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Niu
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Qingfu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Yuemin
authors.initials: Y
authors.lastname: Nan
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D007328:Insulin / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics*; D056971:Nuclear Receptor Co-Repressor 1 / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D007328:Insulin; D035683:MicroRNAs; C534780:Mirn199 microRNA, mouse; C539128:Ncor1 protein, mouse; D056971:Nuclear Receptor Co-Repressor 1; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases