title: miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty liver disease by targeting HMGCR.
abstract: Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health issue with a prevalence of 15-30% in Western populations and 6-25% in Asian populations. Certain studies have revealed the alteration of microRNA (miRNA or miR) profiles in NAFLD and it has been suggested that miR-21 is associated with NAFLD. In the present study, we measured the serum levels of miR-21 in patients with NAFLD and also performed in vitro experiments using a cellular model of NAFLD to further investigate the effects of miR-21 on triglyceride and cholesterol metabolism. Furthermore, a novel target through which miR-21 exerts its effects on NAFLD was identified. The results revealed that the serum levels of miR-21 were lower in patients with NAFLD compared with the healthy controls. In addition, 3-hydroxy-3-methylglutaryl-co-enzyme A reductase (HMGCR) expression was increased in the serum of patients with NAFLD both at the mRNA and protein level. To mimic the NAFLD condition in vitro, HepG2 cells were treated with palmitic acid (PA) and oleic acid (OA). Consistent with the results obtained in the in vivo experiments, the expression levels of miR-21 were decreased and those of HMGCR were increased in the in vitro model of NAFLD. Luciferase reporter assay revealed that HMGCR was a direct target of miR-21 and that miR-21 exerted an effect on both HMGCR transcript degradation and protein translation. Furthermore, the results from the in vitro experiments revealed that miR-21 decreased the levels of triglycerides (TG), free cholesterol (FC) and total cholesterol (TC) in the PA/OA-treated HepG2 cells and that this effect was attenuated by HMGCR overexpression. Taken together, to the best of our knowledge, the present study is the first to report that miR-21 regulates triglyceride and cholesterol metabolism in an in vitro model of NAFLD, and that this effect is achieved by the inhibition of HMGCR expression. We speculate that miR-21 may be a useful biomarker for the diagnosis and treatment of NAFLD.
authors.affiliation: Department of Emergency Medicine, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Chuanzheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Emergency Medicine, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Feizhou
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Emergency Medicine, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Xunyang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Emergency Medicine, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Emergency Medicine, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Mingshi
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Emergency Medicine, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Gui
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Emergency Medicine, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Huaizheng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Emergency Medicine, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Liangkan
authors.initials: L
authors.lastname: Liao
mesh_terms: D020413:3' Untranslated Regions; D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism*; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases