RRC ID 38507
Author Kida K, Nakajima M, Mohri T, Oda Y, Takagi S, Fukami T, Yokoi T.
Title PPARα is regulated by miR-21 and miR-27b in human liver.
Journal Pharm Res
Abstract PURPOSE: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.
Volume 28(10)
Pages 2467-76
Published 2011-10-1
DOI 10.1007/s11095-011-0473-y
PMID 21562928
MeSH 3' Untranslated Regions Cell Line, Transformed Cell Line, Tumor Gene Expression Regulation* HEK293 Cells HeLa Cells Hep G2 Cells Humans Liver / metabolism Liver / physiology* MicroRNAs / genetics* MicroRNAs / metabolism PPAR alpha / genetics* PPAR alpha / metabolism RNA, Messenger / genetics Transfection
IF 3.242
Times Cited 87
Human and Animal Cells HuH-7(RCB1366) Hep G2