TMEM49-related apoptosis and metastasis in ovarian cancer and regulated cell death

Mol Cell Biochem. 2016 May;416(1-2):1-9. doi: 10.1007/s11010-016-2684-3. Epub 2016 Mar 29.

Abstract

Ovarian cancer is one of the greatest causes of cancer death in women. The association of TMEM49 and ovarian cancer is poorly defined. Here, we reported that TMEM49 was significantly increased in ovarian tumor tissues compared to ovarian normal tissues. Furthermore, down-regulation of TMEM49 through RNA interference inhibited cell proliferation and arrested G1/S transition in two ovarian cancer cell lines, OVCAR3 and A2780. More importantly, TMEM49 silencing induced cell apoptosis. Additionally, down-regulation of TMEM49 in ovarian cancer notably repressed cell invasion and adhesion. Further gene set enrichment analysis suggested that apoptosis and metastasis up related signal pathways were associated with the TMEM49 expression. Western blot revealed that the expression of Caspase3, Bad, and Bax were increased, while expression of MMP2, KLF10, and CXCL12 were reduced by TMEM49 knockdown. Since expression of TMEM49 seems to be associated with the apoptosis and metastasis up signaling pathways of ovarian cancer, and suppression of its expression can inhibit cancer cell growth and metastasis, TMEM49 may be a potential therapeutic target in human ovarian cancer.

Keywords: Apoptosis; Invasion; Ovarian cancer; Proliferation; TMEM49.

MeSH terms

  • Apoptosis*
  • Cell Line, Tumor
  • Female
  • G1 Phase Cell Cycle Checkpoints*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • S Phase Cell Cycle Checkpoints*
  • Signal Transduction*

Substances

  • Membrane Proteins
  • Neoplasm Proteins
  • VMP1 protein, human