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Overexpression of SPAG5 Drives In-Vitro Endometrial Cancer Progression via Activating the PI3K/AKT Pathway

JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS(2023)

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摘要
Background: Though sperm-associated antigen 5 (SPAG5) is highly expressed during the tumorigenesis and progression of various cancers, the impact of SPAG5 upon the most prevalent gynecologic cancer, endometrial cancer (EC), remains undefined. This study aims to investigate the impact of SPAG5 on EC cells.Methods: SPAG5 expression in EC tissues and its correlation with the overall survival of EC patients were inspected by bioinformatics. Exogenously upregulating or downregulating SPAG5 expression in EC cells was realized via transfection. Examination of EC cell viability, invasion, migration and apoptosis was accomplished by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl2-H-tetrazolium bromide (MTT), Transwell and scratch assays and flow cytometry. Western blot and quantitative real-time polymerase chain reaction were used to measure the expression levels of SPAG5 and mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) pathway-associated proteins and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-linked markers in EC cells. Results: High expression pattern of SPAG5 was observed in EC tissues (p < 0.05) and cells (p < 0.001), and was associated with a shorter survival time of EC patients. SPAG5 expression was successfully upregulated and downregulated via transfection with SPAG5 overexpression plasmid and shSPAG5, respectively (p < 0.01). Overexpression of SPAG5 increased the viability, migration, and invasion, reduced the apoptosis, and elevated the levels of phosphorylated (p)-AKT, p-PI3K, p-AKT/AKT and p-PI3K/PI3K. SPAG5 downregulation resulted in the opposite results (p < 0.05). However, changes in SPAG5 expression were not correlated with the level of p-ERK or ERK.Conclusion: Overexpression of SPAG5 drives in-vitro EC progression via activating the PI3K/AKT pathway.
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关键词
apoptosis,endometrial cancer,migration/invasion,SPAG5,PI3K / AKT pathway
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