MicroRNAs as key regulators of xenobiotic biotransformation and drug response

摘要

In the last decade, microRNAs have emerged as key factors that negatively regulate mRNA expression. It has been estimated that more than 50 % of protein-coding genes are under microRNA control and each microRNA is predicted to repress several mRNA targets. In this respect, it is recognized that microRNAs play a vital role in various cellular and molecular processes and that, depending on the biological pathways in which they intervene, distorted expression of microRNAs can have serious consequences. It has recently been shown that specific microRNA species are also correlated with toxic responses induced by xenobiotics. Since the latter are primarily linked to the extent of detoxification in the liver by phase I and phase II biotransformation enzymes and influx and efflux drug transporters, the regulation of the mRNA levels of this particular set of genes through microRNAs is of great importance for the overall toxicological outcome. Consequently, in this paper, an overview of the current knowledge with respect to the complex interplay between microRNAs and the expression of biotransformation enzymes and drug transporters in the liver is provided. Nuclear receptors and transcription factors, known to be involved in the transcriptional regulation of these genes, are also discussed.