Reduced expression of SIRT2 in serous ovarian carcinoma promotes cell proliferation through disinhibition of CDK4 expression

Mol Med Rep. 2017 Apr;15(4):1638-1646. doi: 10.3892/mmr.2017.6183. Epub 2017 Feb 8.

Abstract

The silent information regulator 2 related enzyme 2 (SIRT2) has been reported to have an important role in tumorigenesis. Although two distinct effects of SIRT2 have recently been revealed, which explain opposing expression patterns in different types of cancer, the specific function of SIRT2 in ovarian cancer remains unknown. The present study investigated the expression of SIRT2 in serous ovarian carcinoma (SOC) and its pathogenic mechanism. It was observed that SIRT2 expression in SOC was significantly downregulated when compared with ovarian surface epithelium via western blot and immunohistochemistry. Statistical analysis revealed that attenuated expression of SIRT2 was associated with the International Federation of Gynecology and Obstetrics classification of ovarian cancer. Reduced SIRT2 expression during tumorigenesis failed to repress cyclin‑dependent kinase 4 expression, which eventually led to accelerated cell proliferation. Furthermore, the wound healing assay and Transwell assay determined that reduced expression of SIRT2 promoted SOC cell migration and invasion. In conclusion, the results of the current study suggest that SIRT2 has a tumor‑suppressor function in ovarian cells and it might be a viable target for further SOC treatment.

MeSH terms

  • Adult
  • Aged
  • Cell Movement
  • Cell Proliferation
  • Cyclin-Dependent Kinase 4 / metabolism*
  • Cystadenocarcinoma, Serous / genetics*
  • Cystadenocarcinoma, Serous / pathology
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Sirtuin 2 / genetics*
  • Sirtuin 2 / metabolism

Substances

  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Sirtuin 2