caa a22 4500 445313099 CHVBK 20180317142637.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s11095-011-0473-y doi (NATIONALLICENCE)springer-10.1007/s11095-011-0473-y PPARα Is Regulated by miR-21 and miR-27b in Human Liver [Elektronische Daten] [Katsuhiko Kida, Miki Nakajima, Takuya Mohri, Yuki Oda, Shingo Takagi, Tatsuki Fukami, Tsuyoshi Yokoi] 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. Springer Science+Business Media, LLC, 2011 lipid metabolism nationallicence microRNA nationallicence post-transcriptional regulation nationallicence PPARα nationallicence ACS : acyl-CoA synthetase nationallicence AsO : antisense LNA/DNA oligonucleotide nationallicence DMEM : Dulbecco's modified Eagle's medium nationallicence FBS : fetal bovine serum nationallicence IL-6 : interleukin-6 nationallicence LNA : locked nucleic acid nationallicence miRNA : microRNA nationallicence MRE : miRNA recognition element nationallicence PPAR : peroxisome proliferator-activated receptor nationallicence RXR : retinoid X receptor nationallicence Stat3 : signal transducer and activator of transcription 3 nationallicence Kida Katsuhiko Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut Nakajima Miki Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut Mohri Takuya Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut Oda Yuki Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut Takagi Shingo Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut Fukami Tatsuki Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut Yokoi Tsuyoshi Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2467-2476 0724-8741 28:10<2467 2011 28 11095 https://doi.org/10.1007/s11095-011-0473-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0473-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kida Katsuhiko Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut NATIONALLICENCE 700 1- Nakajima Miki Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut NATIONALLICENCE 700 1- Mohri Takuya Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut NATIONALLICENCE 700 1- Oda Yuki Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut NATIONALLICENCE 700 1- Takagi Shingo Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut NATIONALLICENCE 700 1- Fukami Tatsuki Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut NATIONALLICENCE 700 1- Yokoi Tsuyoshi Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, 920-1192, Kanazawa, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2467-2476 0724-8741 28:10<2467 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer