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Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: We found that PPAR[alpha] in human liver is regulated by miRNAs.

(C)2011 Kluwer Academic Publishers