microRNAs as mediators of drug toxicity

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug-Related Side Effects and Adverse Reactions / genetics*
  • Humans
  • Inactivation, Metabolic / genetics*
  • MicroRNAs / genetics*
  • Receptors, Cytoplasmic and Nuclear / genetics*

Substances

  • MicroRNAs
  • Receptors, Cytoplasmic and Nuclear