IBSP激活NF-κB通路促胶质母细胞瘤恶性进展

IBSP promotes glioblastoma progression by activating NF⁃κB signaling

目的:探讨整合素结合唾液酸蛋白(integrin binding sialoprotein,IBSP)在胶质母细胞瘤(glioblastoma,GBM)中的表达与患者临床预后的相关性及其对肿瘤细胞增殖、侵袭及化疗耐药性的调控作用。方法:应用公共数据库系统分析IBSP在GBM中的表达及其与患者预后的关系。在GBM细胞中敲低或过表达IBSP后,功能实验评估细胞增殖、侵袭和化疗耐药性。结果:数据库分析发现IBSP在GBM中的表达水平显著增高,且高水平IBSP提示患者预后较差。敲低IBSP抑制GBM细胞增殖、侵袭,降低化疗耐药性,过表达IBSP促进GBM细胞增殖、侵袭,提高化疗耐药性。过表达IBSP可激活NF-κB通路,上调NF-κB下游基因表达,进而促进GBM细胞的恶性表型。结论:IBSP通过激活NF-κB信号通路促进GBM细胞增殖、侵袭和化疗耐药,提示IBSP可作为GBM潜在治疗靶点。

Objective:To investigate the correlation between the expression of integrin binding sialoprotein(IBSP)in glioblastoma(GBM)and the clinical prognosis of patients,and its regulatory effect on tumor cell proliferation,invasion and chemotherapy resistance.Methods:A public database was used to analyze the expression of IBSP in GBM and its relationship with the prognosis of patients.After IBSP was knockdown or overexpressed in GBM cells,functional assays were used to assess cell proliferation,invasion,and chemoresistance.Results:Database analysis showed that the expression level of IBSP in GBM was significantly increased,and the high level of IBSP indicated a poor prognosis.Knockdown of IBSP inhibited GBM proliferation,invasion and chemoresistance,and overexpression of IBSP promoted GBM proliferation,invasion and chemoresistance.Overexpression of IBSP promoted the activation of NF⁃κB pathway and the expression of downstream genes of NF⁃κB,which in turn promoted the malignant phenotype of GBM cells.Conclusion:IBSP promotes GBM cell proliferation,invasion and chemoresistance by activating the NF⁃κB signaling pathway,suggesting that IBSP can be used as a potential therapeutic target for GBM.