Knockdown of astrocyte elevated gene-1 inhibited cell growth and induced apoptosis and suppressed invasion in ovarian cancer cells

Gene. 2017 Jun 15:616:8-15. doi: 10.1016/j.gene.2017.03.024. Epub 2017 Mar 18.

Abstract

Emerging evidence has demonstrated that AEG-1 (astrocyte elevated gene-1) plays a pivotal oncogenic role in tumorigenesis. However, the molecular mechanism by which AEG-1 exerts its oncogenic function is elusive in ovarian cancer. To explore the role and molecular insight on AEG-1-mediated tumorigenesis in ovarian cancer, multiple approaches are performed including MTT assay, flow cytometry for apoptosis and cell cycle assay, gene transfection, real-time RT-PCR, Western blotting, and Transwell assay. Our MTT assay showed that knockdown of AEG-1 by its siRNA significantly inhibited cell growth in ovarian cancer cells. Moreover, AEG-1 siRNA treatment induced G0/G1 cell cycle arrest and triggered cell apoptosis in ovarian cancer cells. Notably, inhibition of AEG-1 suppressed cell migration and invasion in ovarian cancer cells. Intriguingly, we identified that knockdown of AEG-1 remarkably inhibited the activation of Akt pathway. Our results also validated that knockdown of AEG-1 inhibited the expression of MMP-2 and VEGF, which could lead to inhibition of cell migration and invasion. These data suggest that AEG-1 could be a potential therapeutic target for the treatment of ovarian cancer.

Keywords: AEG-1; Apoptosis; Invasion: pAkt; Ovarian cancer; Proliferation.

MeSH terms

  • Apoptosis
  • Cell Adhesion Molecules / genetics*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques / methods*
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Membrane Proteins
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Small Interfering / pharmacology*
  • RNA-Binding Proteins
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Proto-Oncogene Proteins c-akt
  • MMP2 protein, human
  • Matrix Metalloproteinase 2