title: PPARα is regulated by miR-21 and miR-27b in human liver.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor α (PPARα) is an important transcriptional factor that regulates genes encoding endo/xenobiotic enzymes and lipid metabolizing enzymes. In this study, we investigated whether microRNAs (miRNAs) are involved in the regulation of PPARα in human liver.
  
  
  METHODS
  Precursor or antisense oligonucleotide for miR-21 or miR-27b was transfected into HuH7 cells; expression of PPARα and acyl-CoA synthetase M2B was determined by Western blot and real-time RT-PCR. Luciferase assay was performed to identify the functional miRNA recognition element (MRE). Expression levels of PPARα, miR-21, and miR-27b in a panel of 24 human livers were determined.
  
  
  RESULTS
  The overexpression and inhibition of miR-21 or miR-27b in HuH7 cells significantly decreased and increased the PPARα protein level, respectively, but not PPARα mRNA level. The miRNA-dependent regulation of PPARα affected the expression of its downstream gene. Luciferase assay identified a functional MRE for miR-21 in the 3'-untranslated region of PPARα. In human livers, the PPARα protein levels were not correlated with PPARα mRNA, but inversely correlated with the miR-21 levels, suggesting a substantial impact of miR-21, although the contribution of miR-27b could not be ruled out.
  
  
  CONCLUSIONS
  We found that PPARα in human liver is regulated by miRNAs.
authors.affiliation: Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kida
authors.forename: Miki
authors.initials: M
authors.lastname: Nakajima
authors.forename: Takuya
authors.initials: T
authors.lastname: Mohri
authors.forename: Yuki
authors.initials: Y
authors.lastname: Oda
authors.forename: Shingo
authors.initials: S
authors.lastname: Takagi
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Fukami
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yokoi
mesh_terms: D020413:3' Untranslated Regions; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C524940:MIRN21 microRNA, human; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D047493:PPAR alpha; D012333:RNA, Messenger