SLC4A3通过调控NF-κB信号通路促进胶质母细胞瘤的生长和上皮间质转化  

SLC4A3 Promotes Glioblastoma Growth and Epithelial-mesenchymal Transformation by Regulating the NF-κB Signaling Pathway

作　　者：程功 高论 刘骏辉 CHENG Gong;GAO Lun;LIU Junhui(Department of Critical Care Medicine,The People′s Hospital of Honghu City,Hubei 433200,China)

机构地区：[1]洪湖市人民医院重症医学科,433200 [2]武汉大学人民医院神经外科,430060

出　　处：《医学研究杂志》2025年第3期40-46,共7页Journal of Medical Research

基　　金：国家自然科学基金资助项目(82203136)。

摘　　要：目的探讨溶质载体家族4,成员3(solute carrier family 4,member 3,SLC4A3)在胶质母细胞瘤(glioblastoma,GBM)中的生物学功能和相关的分子机制。方法利用免疫组化分析30例GBM和10例正常脑组织中的SLC4A3表达差异,Kaplan-Meier生存分析评估SLC4A3对GBM患者预后的影响。利用shRNA敲低U87和U251细胞中SLC4A3的表达,然后检测敲低后GBM细胞增殖、迁移和侵袭能力水平的变化,并利用Western blot法检测敲低SLC4A3前后上皮间质转化(epithelial-mesenchymal transition,EMT)和NF-κB信号通路相关蛋白的表达变化。结果SLC4A3在GBM中过表达,高表达的SLC4A3与不良预后相关。敲低SLC4A3抑制了U87和U251细胞的增殖、迁移和侵袭能力,EMT相关蛋白N-cadherin和Vimentin表达水平下调,E-cadherin的表达水平增加。此外,敲低SLC4A3抑制了NF-κB信号通路,进一步发现NF-κB p65的核转位受到抑制。结论SLC4A3通过调控NF-κB p65的核转位影响NF-κB信号通路来调节GBM细胞的生长和EMT,是GBM的新型预后生物学标志物。Objective To investigate the biological function and molecular mechanism of solute carrier family 4,member 3(SLC43)in glioblastoma(GBM).Methods The expression difference of SLC4A3 in 30 GBM and 10 normal brain tissues were analyzed by immunohistochemistry.Kaplan-Meier survival analysis was used to evaluate the effect of SLC4A3 on the prognosis of GBM patients.The expression of SLC4A3 in U87 and U251 cells was reduced by shRNA,and the changes in the proliferation,migration and invasion ability of GBM cells were detected after the knockdown,and Western blot was used to investigate the expression of epithelial-mesenchymal transition(EMT)and NF-κB signaling pathway related proteins after SLC4A3 knockdown.Results SLC4A3 was overexpressed in GBM,and high expression of SLC4A3 was associated with poor prognosis.Knocking down SLC4A3 inhibited the proliferation,migration and invasion of U87 and U251 cells,and the expression levels of N-cadherin and Vimentin were down-regulated,while the expression levels of E-cadherin were increased.In addition,knocking down SLC4A3 inhibited the NF-κB signaling pathway and further found that nuclear translocation of NF-κB p65 was inhibited.Conclusion SLC4A3mediates the NF-κB signaling pathway by regulating the nuclear translocation of NF-κB p65 to influence the growth and EMT of GBM cells,which is a novel prognostic biomarker for GBM.

关 键 词：SLC4A3 GBM 增殖 EMT NF-ΚB信号通路 

分 类 号：R739.41[医药卫生—肿瘤]