Investigating The Feasibility Of Using CBX3 As A Target For Treating Patients With Osteosarcoma

Osteosarcoma has been lacking new chemotherapeutic targets due to its complex genotype and heterogeneity.CBX3 plays an important role in heterochromatin formation,transcriptional regulation,DNA repair,the cell cycle,and telomere maintenance.However,the mechanism of action of CBX3 in osteosarcoma remains unknown.The aim of this study was to investigate the role played by CBX3 in osteosarcoma.CBX3 was upregulated in most tumors in the GTE,TCGA,and TARGET databases.Furthermore,CBX3 upregulation was confirmed by data analysis of GSE42352(GEO database)and RT-q PCR analysis of CBX3 in the Hfob1.9 osteoblast cell line and four osteosarcoma cell lines.CCK8 and scratch migration assays showed that CBX3 deletion significantly inhibited the progression of osteosarcoma cell lines.CBX3-deficient osteosarcoma cells in the G2 phase were blocked and had significantly higher apoptosis rates.Gene expression profiling of CBX3-deficient osteosarcoma cells revealed activation of the anti-DNA damage pathway,apoptosis,and the p53 pathway.Immunofluorescence,protein blotting,and flow-through apoptosis assays demonstrated that CBX3 deletion led to the accumulation of osteosarcoma γH2X and activated the ATR-CHK1-p53 pathway,ultimately leading to the apoptosis of tumor cells.Furthermore,CBX3 deletion reduced the deposition of the gene transcriptional repressor marker H3K9me3 near the BAX promoter region,which contributes to the transcriptional activation of BAX.The deletion of CBX3 also enhanced the inhibitory effect of cisplatin on osteosarcoma cells.CBX3 exhibited potential as a target for osteosarcoma chemotherapy,and the combination of anti-CBX3 and chemotherapeutic agents could be possible.In conclusion,our results suggest that CBX3 promotes osteosarcoma progression by promoting osteosarcoma genome stabilization and anti-apoptosis.