Reactive Oxygen Species Regulate ERBB2 and ERBB3 Expression via miR-199a/125b and DNA Methylation

EMBO Rep. 2012 Dec;13(12):1116-22. doi: 10.1038/embor.2012.162. Epub 2012 Nov 13.

Abstract

Overexpression of ERBB2 or ERBB3 is associated with cancer development and poor prognosis. In this study, we show that reactive oxygen species (ROS) induce both ERBB2 and ERBB3 expression in vitro and in vivo. We also identify that miR-199a and miR-125b target ERBB2 and/or ERBB3 in ovarian cancer cells, and demonstrate that ROS inhibit miR-199a and miR-125b expression through increasing the promoter methylation of the miR-199a and miR-125b genes by DNA methyltransferase 1. These findings reveal that ERBB2 and ERBB3 expression is regulated by ROS via miR-199a and miR-125b downregulation and DNA hypermethylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allantois / growth & development
  • Animals
  • Cell Line, Tumor / drug effects
  • Chickens
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation / drug effects
  • Female
  • Fluoresceins / chemistry
  • Fluoresceins / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Promoter Regions, Genetic / drug effects
  • Reactive Oxygen Species* / chemistry
  • Reactive Oxygen Species* / metabolism
  • Receptor, ErbB-2* / genetics
  • Receptor, ErbB-2* / metabolism
  • Receptor, ErbB-3 / genetics*

Substances

  • Fluoresceins
  • MIRN125 microRNA, human
  • MicroRNAs
  • Reactive Oxygen Species
  • mirn199 microRNA, human
  • diacetyldichlorofluorescein
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • ERBB2 protein, human
  • ERBB3 protein, human
  • Receptor, ErbB-2
  • Receptor, ErbB-3