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第44卷第12期             尹建星,成张淳,王协锋,等. IBSP激活NF⁃κB通路促胶质母细胞瘤恶性进展[J].
                 2024年12月                    南京医科大学学报(自然科学版),2024,44(12):1662-1670                      ·1665 ·


                A          Rembrandt        15   Gravendeel      B              **
                     Relative IBSP expression 15 5  Relative IBSP expression  10 5  Relative IBSP expression 12 8 4
                                                    **
                             **
                      10





                       0                     0                        0
                                                                         NHA  U87 LN229 LN18 T98G  D54
                          NBT  GBM               NBT  GBM
                                                                   **
                                                       Relative IBSP expression 12
                C                                        8
                          NHA  U87  LN229  LN18  T98G  D54  6

                    IBSP                      40 kDa     4
                  GAPDH                       35 kDa     2

                                                         0                                            **
                                                            NHA  U87 LN229 LN18 T98G  D54           **
                                                                                             6
                D                                                                                 **
                                                                       Type
                                               5                                             4
                                                                       Show all   Hide all
                                                                         Astrocytoma  7 608
                                               4                         GBM      40 172   Relative IBSP expression  2
                                                                         Oligodendroglioma 12 048
                 UMAP_2                        3 Expression of IBSP      Recurrent GBM  40 172  0
                                               2                                            -2
                                                                                                    Oligodendroglioma
                                                                                              Recurrent GBM
                                               1                                               GBM  Astrocytoma
                                               0
                                                            UMAP_1
                             UMAP_1
                E          TCGA                     CGGA                   Rembrandt                Gravendeel
                            **                       **                       **                       **
                               **           8           **                       **                      **
                  15
                 Relative IBSP expression  10 5 0  Relative IBSP expression 10 6 4 2  Relative IBSP expression 15 5  Relative IBSP expression 15 5
                                                                    10
                                                                                             10




                  -5
                       Ⅱ    Ⅲ    Ⅳ         -2 0  Ⅱ   Ⅲ    Ⅳ          0   Ⅱ    Ⅲ    Ⅳ         0    Ⅱ    Ⅲ    Ⅳ
                           Grade                    Grade                    Grade                    Grade
                   A:The expression of IBSP in normal brain tissues(NBT)and glioblastoma(GBM)samples from Rembrandt(NBT,n=28,GBM,n=219)and Grav⁃
                endeel(NBT,n=8,GBM,n=159). B:qRT⁃PCR results of IBSP expression in NHA,U87,LN229,LN18,T98G,and D54 cells(n=3). C:Western blot
                results of IBSP expression in NHA,U87,LN229,LN18,T98G,and D54 cells. D:The expression of IBSP in glioma samples from single cell dataset
               (GSE182109)showed by UMAP plot. E:The expression of IBSP in different grade samples from TCGA(gradeⅡ,n=226,gradeⅢ,n=244,gradeⅣ,n=
                150),CGGA(gradeⅡ,n=291,gradeⅢ,n=334,gradeⅣ,n=388),Rembrandt(gradeⅡ,n=98,gradeⅢ,n= 85,gradeⅣ,n=130),and Gravendeel(grade
                                           **
                Ⅱ,n=24,gradeⅢ,n=85,gradeⅣ,n=159). P < 0.01.
                                               图1 IBSP在GBM样本及细胞系中的表达
                                       Figure 1 The expression of IBSP in GBM samples and cell lines

                IBSP敲低则导致细胞凋亡水平显著增高(P < 0.05,                     2.5  IBSP激活NF⁃κB信号通路
                图4H)。Western blot检测发现,过表达IBSP可显著                      利用 TCGA 数据进行基因集富集分析(gene set
                缩短敏感细胞中凋亡标志物γ⁃H2AX 的表达时间,                         enrichment analysis,GSEA)分析发现,IBSP表达水平
                而敲低ISBP可显著延长γ⁃H2AX的表达时间(图4I、                      与NF⁃κB信号通路激活显著正相关(P < 0.05,图5A),
                J)。上述结果提示,IBSP可促GBM化疗耐药。                          提示 IBSP 可能通过激活 NF⁃κB 信号通路维持 GBM
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