Overexpression of PRC1 indicates a poor prognosis in ovarian cancer

Int J Oncol. 2020 Mar;56(3):685-696. doi: 10.3892/ijo.2020.4959. Epub 2020 Jan 10.

Abstract

Protein regulator of cytokinesis‑1 (PRC1) is a microtubule‑associated factor involved in cytokinesis. Recent studies have indicated that PRC1 overexpression is involved in tumorigenesis in multiple types of human cancer. However, the expression, biological functions and the prognostic significance of PRC1 in ovarian cancer have not yet been clarified. In this study, it was confirmed that the PRC1 mRNA and protein expression levels were upregulated in high‑grade serous ovarian carcinoma (HGSOC) tissues, particularly in patients without breast cancer susceptibility gene (BRCA) pathogenic mutations. PRC1 overexpression contributed to drug resistance, tumor recurrence and a poor prognosis. The findings also indicated that PRC1 knockdown decreased the proliferation, metastasis and multidrug resistance of ovarian cancer cells in vitro. It was also demonstrated that forkhead box protein M1 (FOXM1) regulated the mRNA and protein expression of PRC1. Dual‑luciferase reporter assay and rescue assay confirmed that PRC1 was a direct crucial downstream target of FOXM1. On the whole, the findings of this study confirmed that PRC1 was a major prognostic factor of HGSOC and a promising therapeutic biomarker for the treatment of ovarian cancer.

Keywords: protein regulator of cytokinesis-1; prognosis; drug resistance; breast cancer susceptibility gene; high-grade serous ovarian carcinoma.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / metabolism
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / pathology
  • Drug Resistance, Neoplasm
  • Female
  • Forkhead Box Protein M1 / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Promoter Regions, Genetic

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • PRC1 protein, human