Dub3 expression correlates with tumor progression and poor prognosis in human epithelial ovarian cancer

Biomed Pharmacother. 2015 Mar:70:84-9. doi: 10.1016/j.biopha.2015.01.015. Epub 2015 Jan 12.

Abstract

Dub3 is a deubiquitinating enzyme. It is highly expressed in tumor-derived cell lines and has an established role in tumor proliferation. However, the role of Dub3 in human ovarian cancer remains unclear. Expression of Dub3 was evaluated in ovarian cancer tissues and cell lines by immunohistochemistry and Western blot analysis. The relationship between Dub3 expression and clinicopathological characteristics was analyzed. Using RNA interference, the effects of Dub3 on cell proliferation and apoptosis were investigated in ovarian cancer cell line. All normal ovary tissues exhibited very little or no Dub3 immunoreactivity. High levels of Dub3 expression were examined by immunohistochemical analysis in 13.3% of cystadenomas, in 30.0% of borderline tumors, and in 58.9% of ovarian carcinomas, respectively. Dub3 expression was significantly associated with lymph node metastasis and clinical staging (P<0.05). Multivariate survival analysis indicated that Dub3 expression was an independent prognostic indicator of the survival of patients with ovarian cancer. Furthermore, the expression of Cdc25A was closely correlated with that of Dub3 in cancer cells and tissues. Knockdown of Dub3 could inhibit the proliferation of ovarian cancer cells and increase cell apoptosis. These data indicate that the Dub3 might be a valuable biomarker for the prediction of ovarian cancer prognosis and Dub3 inhibition might be a potential strategy for ovarian cancer treatment.

Keywords: CDC25A; Dub3; Ovarian cancer; Proliferation.

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Endopeptidases / genetics
  • Endopeptidases / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Lymphoma
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism

Substances

  • Biomarkers, Tumor
  • CDC25A protein, human
  • cdc25 Phosphatases
  • Endopeptidases
  • USP17L2 protein, human