The polycomb group protein EZH2 inhibits lung cancer cell growth by repressing the transcription factor Nrf2

FEBS Lett. 2014 Aug 25;588(17):3000-7. doi: 10.1016/j.febslet.2014.05.057. Epub 2014 Jun 10.

Abstract

EZH2 is a key component of the polycomb PRC2 complex and functions as a histone H3 Lys27 (H3K27) trimethyltransferase. Here we show that EZH2 is down-regulated in human non-small cell lung cancer and low EZH2 expression predicts poor survival. Further we demonstrate that EZH2 inhibits lung cancer cell proliferation and colony formation in vitro and growth in vivo. We found that EZH2 binds to the promoter of Nrf2, where it increases H3K27me3 and represses Nrf2 expression. Finally, Nrf2 seems to be essential for the hyper proliferation of lung cancer cells in the absence of EZH2.

Keywords: Enhancer of zester homolog 2; Histone H3 lysine 27; NF-E2-related factor 2; Non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Enhancer of Zeste Homolog 2 Protein
  • Epigenesis, Genetic*
  • Female
  • Histones / chemistry
  • Histones / metabolism
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Lysine / metabolism
  • Male
  • Methylation
  • Middle Aged
  • NF-E2-Related Factor 2 / genetics*
  • Polycomb Repressive Complex 2 / metabolism*
  • Survival Analysis

Substances

  • Histones
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2
  • Lysine