Hsa-miR-27a is involved in the regulation of CYP3A4 expression in human livers from Chinese Han population

Pharmacogenomics. 2015;16(12):1379-86. doi: 10.2217/pgs.15.82. Epub 2015 Jul 31.

Abstract

Aim: The huge interindividual difference of CYP3A4 expression may contribute to the variability of drug response. Post-transcriptional regulation of CYP3A4 remains elusive although transcriptional regulation has been studied much more clearly. microRNAs (miRNAs) were reported to be one of factors to regulate the expression of CYP3A4 previously.

Materials & methods: Based on the in silico prediction of 3'-UTR-bindind site of microRNA-27a (miR-27a), the transcriptional and post-transcriptional regulation of miR-27a were investigated through luciferase reporter assay, real-time PCR and immunoblot.

Results: The significantly decrease of CYP3A4 3'-UTR-luciferase activity in human embryonic kidney 293 and Hep3B cells was detected after transfected with plasmid that expressed miRNA-27a in luciferase reporter assay. Correlation study was conducted in human livers (n = 26) and significant correlation has been discovered between miRNA-27a and CYP3A4 mRNA and protein level.

Conclusion: Together, these findings suggest that miR-27a might be involved in the regulation of CYP3A4 gene expression.

Keywords: CYP3A4; Chinese Han population; miR-27a; microRNA; post-transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Asian People / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Cytochrome P-450 CYP3A / genetics*
  • Gene Expression / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • HEK293 Cells
  • Humans
  • Liver / metabolism
  • Liver Neoplasms / genetics*
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics

Substances

  • 3' Untranslated Regions
  • MIRN27 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human