Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 56 (3), 685-696

Overexpression of PRC1 Indicates a Poor Prognosis in Ovarian Cancer

Affiliations

Overexpression of PRC1 Indicates a Poor Prognosis in Ovarian Cancer

Hualei Bu et al. Int J Oncol.

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.

Figures

Figure 1
Figure 1
PRC1 is overexpressed in HGSOC. (A and B) PRC1 mRNA expression in SOC samples compared to normal ovary samples and peritoneum tissues from Oncomine. (C) PRC1 mRNA expression of SOC samples compared with normal ovary samples from the TCGA chort. (D) Differential mRNA expression of PRC1 expression in normal FT (n=14) and HGSOC (n=28) tissues was examined by RT-qPCR. (E) PRC1 mRNA expression in SOC with a different invasive ability from Oncomine. (F) PRC1 mRNA expression in borderline ovrian tumors and ovarian cancer from Oncomine. (G and H) The protein expression level and relative protein expression (PRC1/β-actin) of PRC1 in the HGSOC tissues and normal FT tissues were measured by western blot analysis. **P<0.01. PRC1, protein regulator of cytokinesis-1; HGSOC, high-grade serous ovarian carcinoma; FT, fallopian tube.
Figure 2
Figure 2
Association of PRC1 expression with the clinical outcome of patients with HGSOC. (A-D) Overall survival and progression-free survival of patients as regards PRC1 expression (PRC1 high-expression group vs. and low-expression group) in the TCGA cohort analyzed by Kaplan-Meier Plotter. (E) Representative immunohistochemical staining of PRC1 in HGSOC (magnification, ×200). (F) Kaplan-Meier was used to analyze the overall survival of PRC1 in the high-expression group vs. the low-expression group in the cohort. PRC1, protein regulator of cytokinesis-1; HGSOC, high-grade serous ovarian carcinoma.
Figure 3
Figure 3
PRC1 increases the proliferative ability of ovarian cancer cells in vitro. (A and B) Clonogenic assay and growth curve assay were used to examine the effects of PRC1 on the proliferation of ovarian cancer cells. (C and D) Cell cycle-related proteins and the corresponding densitometric analysis in A2780 cells with PRC1 knockdown and overexpression examined by western blot analysis. (E) Cell cycle analysis of PRC1 knockdown in A2780 cells compared with the control cells analyzed by flow cytometry. *P<0.05 and **P<0.01. PRC1, protein regulator of cytokinesis-1.
Figure 4
Figure 4
PRC1 promotes the migration and invasion of ovarian cancer cells in vitro. (A and B) Effects of PRC1 on the migratory and invasive ability of ovarian cancer cells with PRC1 overexpression or knockdown. (C and D) Western blot analysis of EMT-asssociated markers and the corresponding densitometric analysis in PRC1 knockdown A2780 and SKOV3 cells compared with the control cells. (E) Wound healing assay was used to assess the cell motility in PRC1-overexpressing A2780 cells compared to the control cells. *P<0.05 and **P<0.01. PRC1, protein regulator of cytokinesis-1; EMT, epithelial-mesenchymal transition; MMP9, matrix metalloproteinase 9.
Figure 5
Figure 5
PRC1 promotes the multi-drug resistance of ovarian cancer cells in vitro. (A) Expression of PRC1 evaluated by immunohistochemical staining in tissues of patients with second-line platinum-based chemotherapy. (B) PRC1 mRNA expression in patients with information of second-line platinum-based chemotherpay. (C-F) MTT assay was performed to evaluate the changes of IC50 of cisplatin, taxol and LPD in PRC1 knockdown and overexpression cells. (G and H) Western blot and the corresponding densitometric analysis were used to evaluate the changes in the protein levels in the A2780 and SKOV3 cells with PRC1 knockdown. *P<0.05 and **P<0.01. PRC1, protein regulator of cytokinesis-1; LPD, pegylated liposomal doxorubicin; BRCA1, breast cancer 1; PARP1, poly(ADP-ribose) polymerase 1; AURKB, Aurora B kinase.
Figure 6
Figure 6
PRC1 expression is regulated by FOXM1. (A) Immunohistochemical staining of PRC1 and FOXM1 in corresponding HGSOC samples. (B) Correlation analysis of FOXM1 and PRC1 from the TCGA chort. (C and E) Western blot analysis and corresponding densitometric analysis were used to examine the expression of PRC1 following FOXM1 knockdown in SKOV3 and A2780 cells. (D) The mRNA expression of PRC1 following FOXM1 knockdown in SKOV3 and A2780 cells was examined by RT-qPCR. (F and G) Luciferase report assay was used to determine the regulatory association between FOXM1 and PRC1. (H and I) Transwell assay was used to examine the effect on the migratory and invasive ability following PRC1 konckdown in A2780 FOXM1-overexpressing cells. **P<0.01.

Similar articles

See all similar articles

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29. doi: 10.3322/caac.20138. - DOI - PubMed
    1. Nik NN, Vang R, Shih Ie M, Kurman RJ. Origin and pathogenesis of pelvic (ovarian, tubal, and primary peritoneal) serous carcinoma. Annu Rev Pathol. 2014;9:27–45. doi: 10.1146/annurev-pathol-020712-163949. - DOI - PubMed
    1. Jiang W, Jimenez G, Wells NJ, Hope TJ, Wahl GM, Hunter T, Fukunaga R. PRC1: A human mitotic spindle-associated CDK substrate protein required for cytokinesis. Mol Cell. 1998;2:877–885. doi: 10.1016/S1097-2765(00)80302-0. - DOI - PubMed
    1. Mollinari C, Kleman JP, Jiang W, Schoehn G, Hunter T, Margolis RL. PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone. J Cell Biol. 2002;157:1175–1186. doi: 10.1083/jcb.200111052. - DOI - PMC - PubMed
Feedback