title: microRNAs as mediators of drug toxicity.
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.
authors.affiliation: Department of Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-1192, Japan. tyokoi@p.kanazawa-u.ac.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yokoi
authors.forename: Miki
authors.initials: M
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D018160:Receptors, Cytoplasmic and Nuclear