Overexpression of CARMA3 is associated with advanced tumor stage, cell cycle progression, and cisplatin resistance in human epithelial ovarian cancer

Tumour Biol. 2014 Aug;35(8):7957-64. doi: 10.1007/s13277-014-2070-2. Epub 2014 May 16.

Abstract

CARD recruited membrane associated protein 3 (CARMA3) overexpression has been found in several human cancers. However, its expression pattern and biological roles in human ovarian cancers are not clear. In this study, we examined the expression pattern of CARMA3 in 101 ovarian cancer specimens. We found that 52 (51.5 %) showed CARMA3 overexpression. CARMA3 overexpression positively correlated with tumor histology and advanced FIGO stage. CARMA3 depletion in ovarian cancer cell lines A2780 and HO8910 inhibited ovarian cancer cell proliferation and blocked cell cycle progression. CARMA3 depletion also sensitized ovarian cancer cells to cisplatin-induced cytotoxicity. In addition, Western blot showed that CARMA3 depletion downregulated cyclin D1, cyclin E, and Bcl-2 levels. In conclusion, our data provides evidence that CARMA3 is overexpressed in ovarian cancers and associated with advanced stage. CARMA3 regulates the ovarian cancer cell proliferation, cell cycle progression, and chemoresistance.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / pharmacology*
  • CARD Signaling Adaptor Proteins / analysis
  • CARD Signaling Adaptor Proteins / antagonists & inhibitors
  • CARD Signaling Adaptor Proteins / physiology*
  • Carcinoma, Ovarian Epithelial
  • Cell Cycle
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Cyclin D1 / analysis
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Ovary / chemistry
  • RNA, Small Interfering / genetics

Substances

  • Antineoplastic Agents
  • CARD Signaling Adaptor Proteins
  • CARD10 protein, human
  • CCND1 protein, human
  • RNA, Small Interfering
  • Cyclin D1
  • Cisplatin