The Tentative Exploration Of The Expression And Role Of SKA1 In Epithelial Ovarian Cancer

Objective: This study aims to explore the effect of SKA1 on the malignant behavior of epithelial ovarian cancer,and preliminarily investigate the possible molecular mechanism,so as to provide a scientific evidence for in search of potential therapeutic targets for ovarian cancer.Methods: 1.The expression,prognosis,and pathway enrichment of SKA1 in ovarian cancer as well as the nomogram were performed by bioinformatics.2.The expression of SKA1 in normal ovarian epithelial cells and human ovarian cancer cell lines were verified by Western blot and immunohistochemistry.Then,the CCK8 assay,wound healing assay,and flow cytometry were performed to explore the effect of SKA1 knockdown on cell proliferation,migration,cell cycle and apoptosis.Furthermore,the anti-tumor effect of SKA1 silencing combined with cisplatin was assessed by CCK8 and Ed U assays.3.The expression levels of proteins related to AKT-FOXO3 a signaling pathway were detected by Western blot.Results: 1.Bioinformatics analysis showed that SKA1 was upregulated in ovarian cancer,which was negatively correlated with the survival of epithelial ovarian cancer patients.The constructed nomogram showed superior performances in predicting the prognosis of epithelial ovarian cancer patients.In addition,pathway enrichment analysis indicated that SKA1 was involved in cell cycle,FOXO signaling pathway,platinum resistance,etc.2.Western blot indicated that the protein level of SKA1 was significantly higher in ovarian cancer cells than that in normal ovarian epithelial cells.Furthermore,immunohistochemical staining showed that SKA1 was mainly distributed in the cytoplasm of ovarian cancer cell.Real-time quantitative PCR indicated that the expression level of m RNA was significantly decreased after silencing SKA1.CCK8 assay showed that silencing SKA1 markedly inhibited the proliferation of ovarian cancer cells.Similarly,wound healing assay demonstrated that the migratory ability of ovarian cancer cells was suppressed when SKA1 was silenced.Moreover,silencing SKA1 induced G2/M phase arrest and cell apoptosis.CCK8 assay and Ed U revealed that silencing SKA1 significantly promoted the sensitivity of ovarian cancer cells to cisplatin.3.Western blot demonstrated that silencing SKA1 led to an increase of FOXO3 a protein while a decrease of p-AKT protein.Conclusion: SKA1 may promote ovarian cancer progression by activating the AKT-FOXO3 a signaling pathway.Silencing SKA1 promotes the sensitivity of epithelial ovarian cancer cells to cisplatin.SKA1 may serve as a potential therapeutic target for epithelial ovarian cancer.There are totally 15 figures,8 tables and 201 references...