Role of microRNAs in the regulation of drug metabolizing and transporting genes and the response to environmental toxicants.

INTRODUCTION: MicroRNAs (miRNAs) comprise a family of short non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Rapidly growing evidence indicates that miRNAs play a key role in drug (xenobiotic) metabolism. AREAS COVERED: This review summarizes the current knowledge of the role of miRNAs in the regulation of drug (xenobiotic) metabolizing genes and the cellular responses to exposure to exogenous toxicants. The literature search was performed using the PubMed database (up to March 2012). EXPERT OPINION: miRNAs play a major role in control of the proper functioning of the cellular drug metabolizing system. Emerging evidence indicates that exposure to environmental and occupational toxicants and therapeutic drugs may alter the expression of miRNAs, including those that regulate the expression of drug metabolizing genes. This suggests that drug-induced (xenobiotic-induced) miRNA abnormalities may be one of the underlying mechanisms in the pathogenesis of exposure-related pathologies, and that miRNAs may be potential non-invasive biomarkers of exposure and indicators of the severity of tissue injury induced by toxicants. Also, the evaluation of the expression of miRNAs may be applied for the chemical and drug safety assessment. Additionally, differences in the expression of miRNAs that target drug metabolizing genes may be important determinants for inter-individual differences in sensitivity to toxicants and can serve as critical biomarkers for identifying subpopulations sensitive to exposure.