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EPS8 Promotes The Development Of Glioblastoma By Activating The PI3K/Akt Signaling Pathway

Posted on:2021-01-16Degree:MasterType:Thesis
Country:ChinaCandidate:G YangFull Text:PDF
GTID:2404330611452238Subject:Clinical Medicine
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Objective: Glioblastoma(GBM)is the most common central nervous system tumors,recent studies have shown that epidermal growth factor receptor kinase substrate 8(EPS8)abnormal expression in a variety of malignant tumors,and participate in malignant tumor proliferation,migration,invasion,inhibiting apoptosis and angiogenesis of malignant biological behavior.However,the expression level of EPS8 in GBM and its role are rarely studied.In this study,we will explore the expression level and prognostic value of EPS8 in glioblastoma,and further explore its functional and molecular regulation mechanism in GBM.Methods: we predicted the expression level of EPS8 in GBM and its prognostic value in patients with GBM through bioinformatics and multiple online public databases,and the potential molecular regulation mechanism of EPS8 through Gene Set Enrichment Analysis(GSEA).The expression level of EPS8 in GBM tissues and cell lines was detected by immunohistochemical staining and Western blot.Then,the relationship between the clinicopathological features of EPS8 and GBM patients and the prognostic value were analyzed.Then lentivirus was used to interfere with EPS8 expression,and stable cell lines with low EPS8 expression were established.In vitro experiments such as CCK-8,scratch healing test and Transwell test were conducted to verify the role of EPS8 in biological behavior of GBM cells.The effect of EPS8 on the tumorigenesis of GBM was verified in animal experiments.Finally,Western blot was used to detect the expression changes of related proteins in the PI3K/Akt signaling pathway after EPS8 interference.Results: Through biological information to predict EPS8 in GBM high expression,and the prognosis of patients with high EPS8 expression was worse.EPS8 expression level is closely related to these GBM IDH mutation status,EPS8 mainlyenriched in PI3K/Akt signaling pathway.The high expression of EPS8 in GBM tissues and cells was verified by GBM tissue samples and cell levels,and the prognosis of patients with high EPS8 expression was worse.In cell experiments,EPS8 can promote the proliferation,migration and invasion of GBM U87 MG cells.In animal studies,EPS8 promoted tumor formation in nude mice.EPS8 plays a carcinogenic role by activating the PI3K/Akt signaling pathway.Conclusion: Through bioinformatics analysis,clinical tissue sample detection,validation of cell and animal experiments,and exploration of potential molecular mechanisms,we have reason to believe that EPS8 plays a role in promoting cancer in the GBM process,and EPS8 is likely to become a new target for GBM treatment.
Keywords/Search Tags:Glioblastoma, epidermal growth factor receptor kinase substrate 8, prognosis, PI3K/Akt signaling pathway
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