4-Aminobiphenyl suppresses homologous recombination repair by a reactive oxygen species-dependent p53/miR-513a-5p/p53 loop

Toxicology. 2020 Nov:444:152580. doi: 10.1016/j.tox.2020.152580. Epub 2020 Sep 7.

Abstract

4-Aminobiphenyl (4-ABP), a well-known human carcinogen, can cause oxidative DNA damage and induce miR-513a-5p. However, the interplay between miR-513a-5p and DNA damage remains unclear. In our result of ChIP assay, we speculated that p53 as transcription factor could regulate miR-513a-5p expression. In addition, we found that miR-513a-5p-induced by 4-ABP could suppress p53 expression and HR repair activity. On the other hand, the levels of p53, miR-513a-5p, and γH2AX were attenuated by 5 mM N-acetyl-l-cysteine (NAC) pretreatment, indicating that the reactive oxygen species (ROS)-dependent p53-miR-513a-5p was involved in DSB repair in 4-ABP-treated cells. These findings indicated that the ROS/p53/miR-513a-5p/p53 loop axis plays a relevant role in regulating HR repair which may facilitate our understanding of molecular mechanisms regarding how miR-513a-5p impacts DSB repair in 4-ABP-treated cells.

Keywords: 4-Aminobiphenyl; DNA homologous recombination repair; ROS; miR-513a-5p; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminobiphenyl Compounds / toxicity*
  • Carcinogens / toxicity*
  • Cell Line
  • DNA Damage
  • Humans
  • MicroRNAs / genetics*
  • Reactive Oxygen Species / metabolism
  • Recombinational DNA Repair / drug effects*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Aminobiphenyl Compounds
  • Carcinogens
  • MIRN513A1 microRNA, human
  • MicroRNAs
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • 4-biphenylamine