PPARα Is Regulated by miR-21 and miR-27b in Human Liver

Peroxisome proliferator-activated receptor alpha (PPAR alpha) 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 PPAR alpha in human liver. Precursor or antisense oligonucleotide for miR-21 or miR-27b was transfected into HuH7 cells; expression of PPAR alpha 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 PPAR alpha, miR-21, and miR-27b in a panel of 24 human livers were determined. The overexpression and inhibition of miR-21 or miR-27b in HuH7 cells significantly decreased and increased the PPAR alpha protein level, respectively, but not PPAR alpha mRNA level. The miRNA-dependent regulation of PPAR alpha affected the expression of its downstream gene. Luciferase assay identified a functional MRE for miR-21 in the 3'-untranslated region of PPAR alpha. In human livers, the PPAR alpha protein levels were not correlated with PPAR alpha 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. We found that PPAR alpha in human liver is regulated by miRNAs.