Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: Epigenetic mechanisms in environmental toxicology and carcinogenesis

J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2019;37(3):180-214. doi: 10.1080/10590501.2019.1639481. Epub 2019 Jul 15.

Abstract

Environmental exposures to hazardous chemicals are associated with a variety of human diseases and disorders, including cancers. Phase I metabolic activation and detoxification reactions catalyzed by cytochrome P450 enzymes (CYPs) affect the toxicities of many xenobiotic compounds. Proper regulation of CYP expression influences their biological effects. Noncoding RNAs (ncRNAs) are involved in regulating CYP expression, and ncRNA expression is regulated in response to environmental chemicals. The mechanistic interactions between ncRNAs and CYPs associated with the toxicity and carcinogenicity of environmental chemicals are described in this review, focusing on microRNA-dependent CYP regulation. The role of long noncoding RNAs in regulating CYP expression is also presented and new avenues of research concerning this regulatory mechanism are described.

Keywords: biomarker; chemical carcinogenesis; cytochrome P450 (CYP); epigenetics; epigenomics; long noncoding RNA (lncRNA); microRNA.

MeSH terms

  • Carcinogenesis
  • Cytochrome P-450 Enzyme System / genetics*
  • Ecotoxicology
  • Environmental Exposure*
  • Epigenesis, Genetic*
  • Humans
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Xenobiotics / toxicity*

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Xenobiotics
  • Cytochrome P-450 Enzyme System