Down-regulation of G9a triggers DNA damage response and inhibits colorectal cancer cells proliferation

Oncotarget. 2015 Feb 20;6(5):2917-27. doi: 10.18632/oncotarget.2784.


G9a, a histone methyltransferase, is aberrantly expressed in some human tumor types. By comparing 182 paired colorectal cancer and peritumoral tissues, we found that G9a was highly expressed in colorectal cancer (CRC). Overexpression of G9a promoted CRC cells proliferation and colony formation, whereas knockdown of G9a inhibited CRC cells proliferation. Depletion of G9a increased the rate of chromosome aberration, induced DNA double strand breaks and CRC cells senescence. G9a inhibition synergistically increased γH2AX expression induced by topoisomerase I inhibitors and ultimately led to CRC cell death. The findings that down-regulation of G9a triggers DNA damage response and inhibits colorectal cancer cells proliferation may define G9a as potential oncotarget in CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation* / drug effects
  • Cellular Senescence
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • DNA Damage*
  • Down-Regulation
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HT29 Cells
  • Histocompatibility Antigens / genetics
  • Histocompatibility Antigens / metabolism*
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / metabolism
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • RNA Interference
  • Signal Transduction
  • Time Factors
  • Topoisomerase I Inhibitors / pharmacology
  • Transfection
  • Xenograft Model Antitumor Assays


  • H2AX protein, human
  • Histocompatibility Antigens
  • Histones
  • Topoisomerase I Inhibitors
  • EHMT2 protein, human
  • Histone-Lysine N-Methyltransferase