The effects of microRNA on the absorption, distribution, metabolism and excretion of drugs

Abstract

The importance of genetic factors (e.g. sequence variation) in the absorption, distribution, metabolism, excretion (ADME) and overall efficacy of therapeutic agents is well established. Our ability to identify, interpret and utilize these factors is the subject of much clinical investigation and therapeutic development. However, drug ADME and efficacy are also heavily influenced by epigenetic factors such as DNA/histone methylation and non-coding RNAs [especially microRNAs (miRNAs)]. Results from studies using tools, such as in silico miRNA target prediction, in vitro functional assays, nucleic acid profiling/sequencing and high-throughput proteomics, are rapidly expanding our knowledge of these factors and their effects on drug metabolism. Although these studies reveal a complex regulation of drug ADME, an increased understanding of the molecular interplay between the genome, epigenome and transcriptome has the potential to provide practically useful strategies to facilitate drug development, optimize therapeutic efficacy, circumvent adverse effects, yield novel diagnostics and ultimately become an integral component of personalized medicine.

Figure 1

A hypothetical network view on the interactions between miRNA and ADME transcripts. Molecular interactions used were obtained from KEGG pathway and literature. The network contains 189 interactions between miRNA and its target genes, and 381 nodes including120 miRNAs (squares) and 261 ADME genes (circles). Different colours of circles represent different categories of ADME genes as indicated. The visualization of the network was carried our by Cytoscape.