CYP1A1 is a target of miR-892a-mediated post-transcriptional repression

Int J Oncol. 2012 Jul;41(1):331-6. doi: 10.3892/ijo.2012.1418. Epub 2012 Mar 28.

Abstract

Cytochrome P450 1A1 (CYP1A1) is a member of the cytochrome p450 enzyme family, which is involved in the metabolisms of carcinogenic metabolites, such as benzo(a)pyrene. In this study, we identified miR-892a as a negative regulator of CYP1A1 expression. Luciferase assays revealed a sequence in the 3'-untranslated region of CYP1A1 that displayed a perfect match with miR-892a, and revealed that this sequence was a specific miR-892a target site. The overexpression of miR‑892a inhibited the expression of the CYP1A1 protein, and the miR‑892a antagonist increased CYP1A1 expression. Of note, benzo(a)pyrene, a major inducer of CYP1A1 transcription, decreased the expression of miR-892a. Moreover, the miR-892a-induced CYP1A1 repression inhibited the benzo(a)pyrene-mediated decrease in cell viability. These data provide insight into the CYP1A1 regulatory network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Base Pairing
  • Base Sequence
  • Benzo(a)pyrene / pharmacology
  • Carcinogens / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytochrome P-450 CYP1A1 / genetics*
  • Cytochrome P-450 CYP1A1 / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Luciferases, Firefly / biosynthesis
  • Luciferases, Firefly / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Molecular Sequence Data
  • RNA Interference*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Homology, Nucleic Acid
  • Transcription, Genetic
  • Transcriptional Activation / drug effects

Substances

  • 3' Untranslated Regions
  • Carcinogens
  • MIRN892 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Benzo(a)pyrene
  • Luciferases, Firefly
  • CYP1A1 protein, human
  • Cytochrome P-450 CYP1A1