SAR1A Activation Of The PI3K/AKT/GSK-3β Signaling Pathway Promotes Invasion And Migration While Inhibiting Autophagy In Osteosarcoma Cells

Objective:The purpose of this study is to use big data analysis to search for autophagy-related genes(ARGs)associated with prognosis and construct a risk prognosis model.Investigating the impact of small GTPase SAR1 A on the proliferation and migration abilities of osteosarcoma cells.Further exploration of the relationship between SAR1 A and autophagy,as well as its impact on the intrinsic mechanisms of metastasis in osteosarcoma.Method:1.Obtained a large-scale sequencing dataset of patients with and without metastasis of osteosarcoma from a public database.2.Through WGCNA analysis,the modules most related to the clinical traits of metastasis were analyzed,and a risk prediction model was further constructed.The target gene of the study was further screened out,and the expression difference of SAR1 A was detected by immunohistochemistry.3.The proliferation,migration,and invasion abilities of osteosarcoma cells were evaluated using CCK-8,scratch assay,transwell assay,and Western Blot analysis.4.The impact of SAR1 A on autophagy was assessed through Western Blot and immunofluorescence analysis.5.The pathways influenced by SAR1 A were identified through Western Blot analysis.Results:1.The two modules most closely associated with metastasis were analyzed,and an autophagy-related risk model formula was developed: 0.3130 MYC +(-0.5750)PEA15 + 0.2087SAR1 A.This formula has significant clinical implications for the survival and prognosis of patients.2.In tissues obtained from metastatic patients,the expression of SAR1 A was found to be elevated.Low expression of SAR1 A suppressed the proliferation,migration,and invasion of osteosarcoma cell lines,whereas high expression had the opposite effect.3.The expression of SAR1 A increases in metastatic patient tissues.Low SAR1 A expression inhibits the proliferation,migration,and invasion abilities of osteosarcoma cell line MG63,whereas overexpression of SAR1 A in the ZOS osteosarcoma cell line has the opposite effect.Conclusion:We have established a SAR1A-related prognostic model,which has significant clinical implications.In vitro experiments have shown that knocking down SAR1 A promotes autophagy and inhibits the metastasis of osteosarcoma cells,while overexpression has the opposite effect.SAR1 A is a promising new target for osteosarcoma treatment.