title: MicroRNA-613 represses lipogenesis in HepG2 cells by downregulating LXRα.
abstract: BACKGROUND
  MicroRNAs (miRNAs) emerge as new important regulators of lipid homeostasis by regulating corresponding genes. MiR-613 is a newly discovered microRNA, of which the biological function is unknown. A recent report has shown that miR-613 downregulates liver X receptor α (LXRα), a ligand-activated nuclear receptor playing an important role in the regulation of lipid metabolism. The purpose of this study is to explore the effect and the molecular basis of miR-613 on lipogenesis in HepG2 cells.
  
  
  METHODS
  HepG2 cells were transiently transfected with miR-613 mimic or control microRNA. Real time PCR, Western blot, Luciferase reporter assay and Oil Red O staining were employed to examine the expression of LXRα and its target genes involved in lipogenesis, binding site for miR-613 in 3'-untranslated region (3'-UTR) of LXRα mRNA and lipid droplet accumulation in the cells.
  
  
  RESULTS
  MiR-613 dramatically suppressed the expression of LXRα and its target genes including sterol-regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), carbohydrate responsive element-binding protein (ChREBP) and acetyl-CoA carboxylase (ACC). Reporter assay showed that miR-613 directly bound to 3'-UTR of LXRα mRNA. Moreover, miR-613 significantly repressed LXRα-induced lipid droplet accumulation in HepG2 cells. Ectopic expression of LXRα without 3'-UTR markedly attenuated the miR-613-mediated downregulation of LXRα's target genes and LXRα-induced lipid droplet accumulation.
  
  
  CONCLUSIONS
  MiR-613 suppresses lipogenesis by directly targeting LXRα in HepG2 cells, suggesting that miR-613 may serve as a novel target for regulating lipid homeostasis.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhong
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yi-jun
authors.initials: YJ
authors.lastname: Zeng
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Geng-ze
authors.initials: GZ
authors.lastname: Wu
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Hu
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.forename: Feng-tian
authors.initials: FT
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions; D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D000071518:Liver X Receptors; D008156:Luciferases; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D000071518:Liver X Receptors; C561374:MIRN613 microRNA, human; C116385:MLXIPL protein, human; D035683:MicroRNAs; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D051780:Sterol Regulatory Element Binding Protein 1; D008156:Luciferases; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D000103:Acetyl-CoA Carboxylase