Knockdown of EHF inhibited the proliferation, invasion and tumorigenesis of ovarian cancer cells

Mol Carcinog. 2016 Jun;55(6):1048-59. doi: 10.1002/mc.22349. Epub 2015 Aug 10.

Abstract

Ovarian cancer is the most lethal gynecologic malignancy worldwide. ETS homologous factor (EHF), a member of E26 transformation specific (ETS) transcription factors, has been reported overexpressed in ovarian cancer. However, the molecular mechanism underlying the biological function of EHF in ovarian cancer is still unclear. Here, we found that EHF was elevated in ovarian cancer tissues compared with non-tumorous tissues. Moreover, high EHF expression level was correlated with short survival time of patients with ovarian cancer. Knockdown of EHF in ovarian cancer cells, SKOV3 and OVCAR3, significantly inhibited cell proliferation and increased cells population in G1 phase. The proteins promoting cell cycles (Cyclin B1, Cyclin D1, and PCNA) were down-regulated and the protein negatively regulating cell cycle progression (P21) was up-regulated after EHF knockdown. Moreover, inhibition of EHF in ovarian cancer cells dramatically induced cell apoptosis, but impaired cell adhesion and cell invasion. Furthermore, phosphorylation levels of ERK and AKT were notably reduced in EHF knockdown cells. Finally, in vivo data showed that knockdown of EHF inhibited tumor growth in nude mice. Our data indicates that EHF could be a potential prognosis marker for ovarian cancer and work as an oncogene by targeting ERK and AKT signaling, which can serve as a new target for ovarian cancer treatment. © 2015 Wiley Periodicals, Inc.

Keywords: AKT; EHF; MAPK/ERK; invasion; proliferation.

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques / methods*
  • Humans
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Up-Regulation

Substances

  • EHF protein, human
  • Transcription Factors