title: 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.
authors.affiliation: Institute of Medical Systems Biology, Guangdong Medical College, Dongguan, Guangdong, China.
authors.forename: Y
authors.initials: Y
authors.lastname: He
authors.affiliation: Institute for Systems Biology, Seattle, WA, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Chevillet
authors.affiliation: Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND, USA.
authors.forename: G
authors.initials: G
authors.lastname: Liu
authors.affiliation: Institute for Systems Biology, Seattle, WA, USA.
authors.forename: T K
authors.initials: TK
authors.lastname: Kim
authors.affiliation: Institute for Systems Biology, Seattle, WA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Wang
mesh_terms: D065567:Absorption, Physiological / Q000235:genetics*; D001711:Biotransformation / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D019175:DNA Methylation; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D059467:Transcriptome
chemical_list: D026901:Membrane Transport Proteins; D035683:MicroRNAs; D004364:Pharmaceutical Preparations; D018160:Receptors, Cytoplasmic and Nuclear; D003577:Cytochrome P-450 Enzyme System