Role and mechanism of AKAP12 regulation on AMPK/mTOR signaling pathway mediating cell proliferation,apoptosis and invasion in ovarian cancer cells
In order to explore the specific effect of AKAP12 on malignant behavior of ovarian cancer(OV)cells and construct a prognostic risk prediction model of OV based on hub-Genes,bioinformatics technology was employed,and ovarian cancer was used as a keyword to obtain OV-associated genes from the GeneCards database.OV-associated hub-Genes with significant differ-ences were screened through the comprehensive gene expression database(GEO)and their functions were analyzed.The hub-Genes which were significantly related to the overall survival of OV samples were screened by univariate Cox regression analy-sis.LASSO algorithm was used to construct a prognostic risk prediction model for ovarian cancer.Kaplan-Meier(KM)survival curve,univariate and multivariate Cox regression analysis and ROC curve were used to test the predictive ability of this model for OV patients,and SangerBox was used to analyze the correlation between AKAP12 and OV patients'prognosis online.After A KA P1 2 overexpression was achieved,MTT assay was used to detect cell proliferation,flow cytometry was used to detect cell apoptosis,transwell was used to detect cell invasion,and Western blot was used to detect the expression of AMPK signaling pathway-related proteins.The results were as follows:① 8 378 OV-related genes were obtained from GeneCards data base,among which 82 OV-related hub-Genes had significant differences between normal and OV tissues;② An OV risk prediction model based on five hub-Genes(BIRC5,EP-CAM,AKAP12,PDGFRA,CLDN4)was successfully constructed,which could predict the prognosis of patients with OV;③ SangerBox online analysis showed that patients with high AKAP12 expres-sion had worse prognosis;④ The overexpression of AKAP12 can significantly promote cell proliferation and invasion,and in-hibit cell apoptosis;⑤ Overexpression of AKAP12 significantly decreased AMPK phosphorylation and significantly increased mTOR phosphorylation.In conclusion,in this study,the characteristic risk model constructed based on five hub-Genes can effectively predict the prognosis of OV patients.AKAP12 can induce the proliferation and invasion of OV cells through AMPK/mTOR signaling pathway,and inhibit the apoptosis of OV cells.
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