シトクロムP450と転写因子のmicroRNAによる発現制御

MicroRNAs (miRNAs) are endogenous ~22-nucleotide non-coding RNAs that regulate gene expression through the translational repression or degradation of target mRNAs. The human genome contains over 1400 miRNAs and over 60% of human mRNAs are predicted to be targets of miRNAs. The miRNAs have roles in fine-tuning the expression of their target genes forming intricate networks. Research on miRNA is growing exponentially, and it is now clear that miRNAs can potentially regulate every aspect of cellular processes such as differentiation, proliferation and apoptosis as well as a large range of physiological processes such as development, immune response, metabolism, tumor formation, and disease development. The roles of miRNAs in the metabolism of xenobiotics and endobiotics have only recently been revealed. This review describes the current knowledge on the regulation of cytochrome P450s and transcriptional factors by miRNAs, and its physiological and clinical signifficance, which were disclosed in our studies. The miRNA expression is readily altered by chemicals, carcinogens, drugs, hormones, stress, or diseases, and the dysregulation of specific miRNAs might lead to changes in the drug metabolism potency or pharmacokinetics as well as pathophysiological changes. Utilizing miRNAs opens a new era in the fields of drug metabolism and pharmacokinetics as well as toxicology. © 2012 The Pharmaceutical Society of Japan