TM7SF4在胶质母细胞瘤中的表达及生物学功能研究

The expression of TM7SF4 in glioblastoma and its effects on biological functions

目的探讨树突表达特异性7跨膜蛋白(TM7SF4)在胶质母细胞瘤(GBM)中的表达及对增殖、凋亡、肿瘤免疫浸润等生物学功能的影响。方法采用CCK8、流式细胞术、划痕实验、荧光定量PCR(RT-qPCR)分析TM7SF4在GBM中的表达和作用。采用生物信息学分析(包括TIMER、LinkedOmics、DAVID、String、TISIDB和cBioPortal数据库分析)TM7SF4基因的表达、相关差异基因、基因富集和功能分析、免疫细胞浸润等。结果TM7SF4在GBM组织和细胞系中低表达,差异有统计学意义(P<0.01);在GBM细胞U251中干扰TM7SF4基因促进细胞增殖和迁移,抑制细胞凋亡,差异有统计学意义(P<0.01);生物信息学分析TM7SF4表达相关基因主要参与免疫反应和细胞间信号传导等生物过程;TM7SF4的表达与GBM肿瘤免疫浸润B淋巴细胞、CD4^(+)T细胞、CD8^(+)T细胞、巨噬细胞、中性粒细胞、树突状细胞的表达丰度均呈正相关(P<0.05);TM7SF4基因可能与CCR7、CD80、GZMB、CSF2、CD27、CCL4、CD2、CD1C等基因存在相互作用关系。结论TM7SF4在GBM中低表达,干扰TM7SF4能促进GBM细胞增殖和迁移和抑制细胞凋亡,TM7SF4可能是一个潜在的预后生物标志物和免疫治疗靶点。

Objective To investigate the expression of Transmembrane 7 superfamily member 4(TM7SF4)in glioblastoma(GBM)and its effects on biological functions such as proliferation,apoptosis and tumor immune infiltration.Methods The expression and function of TM7SF4 in GBM were identified by CCK8,flow cytometry,scratch test and RT-qPCR analysis.Bioinformatics analysis(including TIMER,LinkedOmics,DAVID,String,TISIDB and cBioPortal)were used to analyze the expression of TM7SF4 gene,related differential genes,gene enrichment and function analysis,immune cell infiltration,etc.Results The expression of TM7SF4 was low in GBM tissues and cell lines than control group(P<0.01).Interfering with TM7SF4 gene promoted the proliferation and migration of GBM cell U251(P<0.01)and inhibited the apoptosis of U251 cell(P<0.01).TM7SF4 expression related genes are mainly involved in biological processes such as immune response and intercellular signal transduction.The expression of TM7SF4 was positively correlated with the expression abundance of immune infiltrating B cells,CD4^(+)T,CD8^(+)T,DC,macrophages and neutrophils in GBM(P<0.05).TM7SF4 gene may interact with CCR7,CD80,GZMB,CSF2,CD27,CCL4,CD2,CD1 C.Conclusion The low expression of TM7SF4 in GBM can promote the proliferation,migration,and inhibit apoptosis of GBM,which may be a potential prognostic biomarker and immu no therapeutic target.