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

Kida, Katsuhiko; Nakajima, Miki; Mohri, Takuya; Oda, Yuki; Takagi, Shingo; Fukami, Tatsuki; Yokoi, Tsuyoshi
October 2011
Pharmaceutical Research;Oct2011, Vol. 28 Issue 10, p2467
Academic Journal
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.


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