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Annu Rev Pharmacol Toxicol. 2013;53:377-400. doi: 10.1146/annurev-pharmtox-011112-140250. Epub 2012 Nov 16.

microRNAs as mediators of drug toxicity.

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1
Department of Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-1192, Japan. tyokoi@p.kanazawa-u.ac.jp

Abstract

microRNAs (miRNAs) represent the most abundant class of gene expression regulators that bind complementarily to transcripts to repress their translation or mRNA degradation. These small ( 21-23 nucleotides in length) noncoding RNAs are derived through a multistep process by miRNA genes located in genomic DNA. Because miRNAs regulate fundamental cellular functions, their dysregulation affects a large range of physiological processes, such as development, immune responses, metabolism, and diseases as well as toxicological outcomes. Cancer-related miRNAs have been extensively studied; however, the roles of miRNAs in xenobiotic metabolism and in toxicology have only recently been explored. This review focuses on the current knowledge of miRNA-dependent regulation of drug-metabolizing enzymes and nuclear receptors and the associated potential toxicological implications. The potential modulation of toxicology-related changes in miRNA expression, the role of miRNA in immune-mediated drug-induced liver injuries, the use of circulating miRNAs in body fluids as potential toxicological biomarkers, and the link between miRNA-related pharmacogenomics and adverse drug reactions are highlighted.

[Indexed for MEDLINE]

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