Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Thus, there is an emergent need to invest a novel therapeutic for EOC. In this study, we defined ubiquitin-specific protease 14 (USP14) as a therapeutic target for EOC. Western blot was used to evaluate the expression of USP14 in nine fresh EOC tissues and three fresh normal ovarian tissues. The protein level of USP14 was higher in the cancer samples compared with that in the normal ovary tissues. Immunohistochemistry analysis was performed on formalin-fixed paraffin-embedded section of 116 cases of EOCs and indicated that USP14 was significantly associated with clinical pathologic variables. Kaplan-Meier curve showed that high expression of USP14 was related to poor prognosis of EOC patients. Starvation and re-feeding assay was used to imitate cell cycle, suggesting that USP14 played a critical role in SKOV3 cell proliferation. CCK-8 assay showed that SKOV3 cells treated with USP14-shRNA (shUSP14) grew more slowly than control group. Flow cytometry revealed that the reduced expression of USP14 induced the apoptosis of the SKOV3 EOC cells. In summary, our findings suggest that USP14 is involved in the progression of EOC and that it may be a useful target of therapy in EOC.
Background/Aims: This study aimed to investigate the expression and prognostic value of kinesin family member 2A (KIF2A) and the suppression effects of microRNA-206 (miR-206) on KIF2A in ovarian cancer. Methods: Ovarian cancer tissues from patients and ovarian cancer cell lines (A2780 and SKOV3) were used in this study. miR-206 mimics and control were transiently transfected into cells. RT-qPCR was performed to detect KIF2A mRNA and miR-206 expression levels, Western blot was performed to detect KIF2A protein levels, Dual-Luciferase Reporter Assay was used to examine the inhibition effects of miR-206 on KIF2A mRNA, immunohistochemical staining was used to examine the expression of KIF2A in tissue sections. CCK-8, transwell and Annexin-V-FITC/Propidium Iodide staining with flow cytometry were used to detect the cell proliferation, migration/invasion, and apoptosis respectively. Results: Our study explored the expression profiles of KIF2A and miR-206 in the patients with ovarian cancer. We found that overexpression of KIF2A was associated with a poor prognosis in ovarian cancer. We also found that KIF2A mRNA contains two target sites for miR-206 binding and confirmed that miR-206 directly suppresses KIF2A; inhibits ovarian cancer cell proliferation, migration, and invasion; and induces apoptosis. Conclusion: The results suggest KIF2A could serve a valuable prognostic indicator in ovarian cancer and provide a rationale for treatment of ovarian cancer by targeting KIF2A via miR-206.
Overexpression of cyclin-dependent kinase 1 (CDK1) has been noted to correlation with several human cancers. However, the effects of CDK1 on ovarian cancer development remain unclear. The aim of this study was to examine the effect of CDK1 and related mechanism in the proliferation and resistance to chemotherapeutic drugs of epithelial ovarian cancer (EOC). Immunohistochemical analysis was performed in 119 human ovarian cancer samples, and the data were correlated with clinicopathologic features. Furthermore, Western blot analysis was performed for CDK1 in EOC samples and cell lines to evaluate their protein levels and molecular interaction. Kaplan-Meier survival analysis showed that strong expression of CDK1 exhibited a significant correlation with poor prognosis in human EOC (P = 0.02). Meanwhile, we found that knockdown CDK1 by shCDK1 promoted the apoptosis rate and increased the sensitivity to chemotherapy drugs. Thus, CDK1 might serve as a prognostic marker, and it might be of great value for experimental therapies in EOC.
Recent investigations have confirmed up-regulation of serum miR-21 and its diagnostic and prognostic value in several human malignancies. In this study, we examined serum miR-21 levels in epithelial ovarian cancer (EOC) patients, and explored its association with clinicopathological factors and prognosis. The results showed significantly higher serum miR-21 levels in EOC patients than in healthy controls. In addition, increased serum miR-21 expression was correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. These findings indicate that serum miR-21 may serve as a novel diagnostic and prognostic marker, and be used as a therapeutic target for the treatment of EOC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.