The involvement of miRNAs in CYP450 gene expression: A brief review of the literature

Abstract

Drug biotransformation is a critical process in metabolic elimination of drugs. It occurs mainly in the liver as well as in other tissues such as kidney and small intestine and consists of three stages: Phase I, Phase II and Phase III. Drugs are converted to a more polar and hydrophilic metabolites during Phase I and Phase II, which are excreted by a variety of membrane transporters such as P-glycoprotein and Multidrug Resistance Protein 1 in Phase III. Cytochrome P450 enzyme isoforms achieve 80% of Phase I metabolism. It is well described that there is inter-individual drug response variability such as adverse drug reactions or reduced drug efficacy and that genetic variation within the sequence of biotransformation-related genes affects these different therapeutic outcomes observed between individuals. However, genetic factors cannot completely explain inter-individual differences. Recent studies have shown that epigenetic factors such as histone modification, DNA methylation and non-coding miRNAs heavily influence drug biotransformation through post-transcriptional regulation of metabolism gene expression. It is important to understand the causes of alterations in drug metabolism since varied biotransformation may lead to adverse drug effects or a loss of efficacy. Therefore, in this review, the effects of miRNAs in CYP450 gene expression will be discussed briefly in the light of recent studies.