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Pharmacol Ther. 2011 Sep;131(3):330-7. doi: 10.1016/j.pharmthera.2011.04.009. Epub 2011 Apr 30.

MicroRNAs from biology to future pharmacotherapy: regulation of cytochrome P450s and nuclear receptors.

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1
Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Japan. nmiki@p.kanazawa-u.ac.jp

Abstract

MicroRNAs (miRNAs) are a family of short, non-coding RNAs whose final product is a 22-nucleotide functional RNA molecule. They regulate the expression of target genes by binding to complementary regions of transcripts to repress their translation or promote mRNA degradation. Since miRNAs regulate every aspect of cellular function, their dysregulation is associated with a variety of diseases including cancer, diabetes, and cardiovascular diseases. Therefore, miRNAs are now considered new therapeutic targets. However, 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 nuclear receptors by miRNAs, the physiological and clinical significance. 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. In the field of pharmacogenomics, the evaluation of miRNA-related polymorphisms would provide useful information for personalized medicine. Utilizing miRNAs opens a new era in the fields of drug metabolism and pharmacokinetics as well as toxicology.

[Indexed for MEDLINE]

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