The Study On Expression And Mechanism Of PNMA5 In Epithelial Ovarian Cancer

Background:Ovarian cancer is one of the common gynecological malignancies The incidence rate is second only to cervical cancer and endometrial cancer.The mortality rate is at the top of gynecological malignancies.The etiology and pathogenesis have not been fully elucidated,and there is no effective early diagnosis method.Most patients have diagnosed at advanced stage at the time of diagnosis and have a poor prognosis.If ovarian cancer can be detected and diagnosed at early stage,it will significantly prolong the survival of patients and improve their prognosis,which has important clinical significance.PNMA5 is a confirmed tumor neuron antigen,and the related neurogenic paraneoplastic syndrome produced by PNMA5 may be an early manifestation of some occult tumors.Studies have shown that PNMA5 plays an important role in maintaining the malignant phenotype of liver cancer cells and the expression of PNMA5 could provide significant prognostic value for colon cancer.but other study show PNMA5 promotes apoptosis signaling in HeLa and MCF-7 cells.Our previous study found that PNMA5 plays an important role in the continuous meiosis of mouse oocytes through a series of phosphorylation However,studies on the relationship between PNMA5 and ovarian cancer have not been studied throughout the worldObjective:To investigate the role of PNMA5 in the development and progression of epithelial ovarian cancer and its molecular mechanism,and try to provide theoretical and experimental basis for the early diagnosis and as a new therapeutic target in epithelial ovarian cancerMethods:1)Immunohistochemistry was used to detect the expression of PNMA5 in epithelial ovarian cancer,benign ovarian tumor and normal ovarian tissue The expression of PNMA5 in ovarian cancer cell line HO8910 and normal ovary cell line Moody was detected by Western-Blot method.2)Using specific PNMA5 siRNA transfection to effectively interfere with the expression of ovarian cancer cell line PNMA5,CCK-8 method for cell proliferation,flow cytometry for cell cycle and apoptosis,cell scratch assay for cell migration,transwell assay for cell invasion ability and cell mitochondria and microfilament changes were detected by Mito Tracker and Rhod-Phalloidin staining.3)Western-Blot and immunofluorescence were used to detect Src?PNMA5?GSK-3? cell signaling pathwayResults:1)The expression of PNMA5 in epithelial ovarian cancer tissues was significantly higher than that in ovarian benign tumors and normal ovarian tissues The positive expression of PNMA5 in epithelial ovarian cancer tissues was closely related to FIGO stage and histological grade of ovarian cancer.2)PNMA5 expression in ovarian cancer cell line HO8910 is higher than that in normal ovarian cell line Moody.3)Specific PNMA5 siRNA transfection can effectively knock down the expression of PNMA5 in ovarian cancer cell line HO8910.4)Knocking down PNMA5 in HO8910 can not only inhibit the proliferation of HO8910 cells,block the cell cycle from G1 to S phase,promote early apoptosis rate,inhibit the migration and invasion of HO8910 cells,but also lead to abnormal distribution and accumulation of mitochondria in HO8910 cells,and inhibit cell actin polymerization.5)Phosphorylation of PNMA5 is positivly regulated by Src phosphorylation,and PNMA5 phosphorylation can positivly regulate downstream GSK-3? signaling pathway.Conclusions:1)PNMA5 plays an important role in the occurrence and development of epithelial ovarian cancer and may be a potential therapeutic target for epithelial ovarian cancer.2)PNMA5 expression can effectively be knocked down in ovarian cancer cell lines HO8910 by gene interference,and which can significantly affect the malignant biological behavior of ovarian cancer cell lines HO8910.3)PNMA5 promotes probably the development and progression of ovarian cancer through Src?PNMA5?GSK-3? signaling pathway activity.