Serglycin Promotes Proliferation,Migration,and Invasion Via The JAK/STAT Signaling Pathway In Osteosarcoma

Background: Osteosarcoma is the most common malignant bone tumor in adolescents under 20 years old,with high metastatic potential and poor prognosis,but its specific pathogenesis is still unclear.The purpose of this study is to screen and analyze the key genes that affect the proliferation,invasion and metastasis of osteosarcoma cells by bioinformatics.Methods: Firstly,the osteosarcoma gene chips GSE124768 and GSE126209 were downloaded from Gene Expression Omnibus(GEO database),and a large number of differentially expressed genes were screened by differential expression analysis with R software and GEO2 R.The functional enrichment of differentially expressed genes was analyzed by Fun Rich software,KEGG signal pathway was analyzed by Cytoscape software,and the protein-protein interaction network map was drawn by String database.Finally,the differential gene Serglycin(SRGN)was screened out.Real-time fluorescence quantitative PCR(q RT-PCR)and Western-blot assays were used to detect the differential expression of SRGN in osteosarcoma cells.After that,knock out SRGN and overexpression SRGN in 143 B cells for functional experiments,functional experiments(including Transwell assays,wound healing assays and CCK-8 assays,etc.)proved that SRGN enhance the invasion of osteosarcoma.Finally,Western-blot experiment was used to explore the mechanism of SRGN in osteosarcoma cells.Results: In this study,352 m RNAs were differentially expressed between osteosarcoma cells and human osteoblasts,and the most suitable gene SRGN was selected.Through Western-blot assays,it was found that the expression level of SRGN in osteosarcoma cells was higher than that in human osteoblasts,and the invasion and proliferation ability of osteosarcoma cells was significantly enhanced after overexpression of SRGN.On the contrary,the invasion and proliferation ability of osteosarcoma cells decreased after knocking down SRGN.In addition,the overexpression of SRGN increased the phosphorylation level of JAK2 and STAT3,and activated the anti-apoptotic gene Bcl-2 to inhibit tumor cell apoptosis.Conclusions: The differentially expressed gene SRGN was screened by bioinformatics analysis,and it was proved that SRGN may enhance the proliferation and invasion of osteosarcoma by affecting JAK/STAT signal pathway,which may provide a new therapeutic target for the treatment of osteosarcoma in the future.