microRNAs as Mediators of Drug Toxicity

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, 22, 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.