Most recent findings on microRNA-dependent regulation of drug metabolism

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  • Nakano Masataka
    WPI Nano Life Science Institute, Kanazawa University Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University
  • Nakajima Miki
    WPI Nano Life Science Institute, Kanazawa University Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University

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  • microRNAによる薬物代謝制御に関する最新知見
  • 創薬シリーズ(8)創薬研究の新潮流(33)microRNAによる薬物代謝制御に関する最新知見
  • ソウヤク シリーズ(8)ソウヤク ケンキュウ ノ シン チョウリュウ(33)microRNA ニ ヨル ヤクブツ タイシャ セイギョ ニ カンスル サイシン チケン

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Abstract

<p>Drug metabolism is an important determinant to control pharmacokinetics, drug response and drug toxicity. Large variabilities are observed in expression or activity of drug-metabolizing enzymes such as cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT). Therefore, understanding of the causes for the variation of drug metabolism potencies is essential for efficient drug development and promotion of safe use of medicines. The expression of drug-metabolizing enzymes is controlled by transcriptional regulation by nuclear receptors and transcriptional factors, and by epigenetic regulation such as DNA methylation and histone acetylation. In addition to such regulatory mechanisms, recent studies revealed that microRNAs (miRNAs) significantly contribute to post-transcriptional regulation of drug-metabolizing enzymes. miRNAs are endogenous ~22-nucleotide non-coding RNAs that regulate gene expression through the translational repression and degradation of mRNAs. More recently, it has been clarified that the presence of pseudogenes or single nucleotide polymorphisms as well as RNA editing event affect miRNA-dependent regulation. It is unwavering fact that miRNAs significantly contribute to inter- and intra-individual differences in the expression of drug-metabolizing enzymes. In this review, we introduce current knowledge of miRNA-mediated regulation of drug metabolism.</p>

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