Current knowledge of microRNA-mediated regulation of drug metabolism in humans

Expert Opin Drug Metab Toxicol. 2018 May;14(5):493-504. doi: 10.1080/17425255.2018.1472237. Epub 2018 May 11.

Abstract

Understanding the factors causing inter- and intra-individual differences in drug metabolism potencies is required for the practice of personalized or precision medicine, as well as for the promotion of efficient drug development. The expression of drug-metabolizing enzymes is controlled by transcriptional regulation by nuclear receptors and transcriptional factors, epigenetic regulation, such as DNA methylation and histone acetylation, and post-translational modification. In addition to such regulation mechanisms, recent studies revealed that microRNAs (miRNAs), endogenous ~22-nucleotide non-coding RNAs that regulate gene expression through the translational repression and degradation of mRNAs, significantly contribute to post-transcriptional regulation of drug-metabolizing enzymes. Areas covered: This review summarizes the current knowledge regarding miRNAs-dependent regulation of drug-metabolizing enzymes and transcriptional factors and its physiological and clinical significance. We also describe recent advances in miRNA-dependent regulation research, showing that the presence of pseudogenes, single-nucleotide polymorphisms, and RNA editing affects miRNA targeting. Expert opinion: It is unwavering fact that miRNAs are critical factors causing inter- and intra-individual differences in the expression of drug-metabolizing enzymes. Consideration of miRNA-dependent regulation would be a helpful tool for optimizing personalized and precision medicine.

Keywords: CYP; Drug metabolism; SULT; UGT; microRNA; post-transcriptional regulation.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Design
  • Enzymes / genetics*
  • Enzymes / metabolism
  • Epigenesis, Genetic
  • Gene Expression Regulation, Enzymologic
  • Humans
  • MicroRNAs / genetics*
  • Pharmaceutical Preparations / metabolism*
  • Precision Medicine / methods
  • Protein Processing, Post-Translational
  • Transcription Factors / genetics

Substances

  • Enzymes
  • MicroRNAs
  • Pharmaceutical Preparations
  • Transcription Factors