B7-H3分子通过SIRT1/p53信号途径抑制非小细胞肺癌细胞凋亡OA
B7-H3 molecule inhibits apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway
目的 探究组蛋白脱乙酰酶Sirtuin-1(SIRT1)/p53信号途径在协同信号分子B7同源药物(B7-H3)抑制非小细胞肺癌(NSCLC)细胞凋亡中的作用.方法 GEPIA 2平台进行基于B7-H3基因表达水平的NSCLC患者的生存分析;基因集富集分析(GSEA)用于分析细胞凋亡基因集合中B7-H3分子的富集特征;在NSCLC的A549细胞系中敲减B7-H3,通过Western blot检测SIRT1和p53的蛋白表达水平;在A549细胞中过表达B7-H3,通过Annexin V/PI双染后流式细胞术分析细胞凋亡率;A549细胞过表达B7-H3并敲减SIRT1,通过Western blot分别检测p53及凋亡相关蛋白B细胞淋巴瘤-2(Bcl-2)和Bcl-2 相关 X 蛋白(Bax)的表达水平,Annexin V/PI双染后流式细胞术分析细胞凋亡率.结果 B7-H3高表达组的总体生存期低于低表达组(P<0.01);B7-H3显著富集在细胞凋亡信号通路及p53信号通路(P<0.05);与对照组相比,B7-H3敲减组的SIRT1蛋白表达下调,p53上调(均P<0.001);而过表达B7-H3上调SIRT1蛋白表达(P<0.05),下调p53表达(P<0.01),凋亡通路相关蛋白Bcl-2与Bax的比值升高(P<0.001);Annexin V/PI双染法结果显示过表达B7-H3(13.87%±0.82%)的A549细胞凋亡率较对照组(26.72%±4.13%)下降(P<0.01);在过表达B7-H3细胞系中,敲减SIRT1逆转细胞凋亡(P<0.05),p53蛋白表达上调(P<0.001),Bcl-2/Bax的比值降低(P<0.001).结论 B7-H3分子通过SIRT1/p53信号途径抑制NSCLC细胞凋亡.
Objective To explore the role of the histone deacetylase Sirtuin-1(SIRT1)/p53 signaling pathway in promoting apoptosis of non-small cell lung cancer cells(NSCLC)induced by the co-stimulatory molecule B7 homo-log 3(B7-H3).Methods The GEPIA 2 platform was used for survival analysis of NSCLC patients based on B7-H3 gene expression levels.The Gene Enrichment Analysis(GSEA)method was used to analyze the enrichment characteristics of B7-H3 molecules in the gene set of cell apoptosis.In the non-small cell lung cancer A549 cell line,B7-H3 was knocked down,and the protein expression levels of SIRT1 and p53 were detected by Western blot.B7-H3 was overexpressed in A549 cells and the apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining.Overexpression of B7-H3 and knockdown of SIRT1 were performed in A549 cell line.The ex-pression levels of p53 and apoptosis-related proteins B-cell lymphoma/leukemia-2(Bcl-2)and Bcl-2-associated X protein(Bax)were detected respectively by Western blot.Cell apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining.Results The overall survival of the B7-H3 high-expression group was significantly lower than that of the low-expression group(P<0.01).B7-H3 was significantly enriched in the cell apoptosis sig-naling pathway and the p53 signaling pathway(P<0.05).Compared with the control group,the expression of SIRT1 was significantly downregulated,and p53 was significantly upregulated in the B7-H3 knockdown group(both P<0.001).Overexpression of B7-H3 significantly up-regulated SIRT1 protein expression(P<0.05),down-regulated p53 expression(P<0.01),and markedly increased the Bcl-2/Bax ratio of apoptosis-related proteins(P<0.001).The results of Annexin V/PI double staining showed that the apoptosis rate of A549 cells with overex-pressed B7-H3 decreased(the apoptosis rate of the control group was 26.72%±4.13%,while that of the B7-H3 overexpression group was 13.87%±0.82%;P<0.01).In B7-H3-overexpressing cell lines,SIRT1 knockdown sig-nificantly reversed apoptosis(P<0.05),up-regulated p53 protein expression(P<0.001),and markedly reduced the Bcl-2/Bax ratio(P<0.001).Conclusion B7-H3 molecule inhibits the apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway.
郑霖;钟剑鑫;牛可;徐晴;凌惠娟;朱亚玉;陈兵;陈礼文
安徽医科大学第二附属医院 临床检验诊断学教研室,合肥 230601安徽医科大学第二临床医学院,合肥 230032安徽医科大学第二附属医院 临床检验诊断学教研室,合肥 230601安徽医科大学第二附属医院 临床检验诊断学教研室,合肥 230601安徽医科大学第二附属医院 临床检验诊断学教研室,合肥 230601安徽医科大学第二附属医院 临床检验诊断学教研室,合肥 230601安徽医科大学第二附属医院 临床检验诊断学教研室,合肥 230601||安徽医科大学第二附属医院 检验科,合肥 230601安徽医科大学第二附属医院 临床检验诊断学教研室,合肥 230601||安徽医科大学第二附属医院 输血科,合肥 230601
医药卫生
非小细胞肺癌细胞凋亡协同信号分子B7-H3SIRT1p53
non-small cell lung cancercell apoptosisco-signalling moleculesB7-H3SIRT1p53
《安徽医科大学学报》 2026 (2)
232-238,7
国家自然科学基金项目(编号:82404970)安徽省高校自然科学研究重点项目(编号:2023AH053170)安徽省临床医学研究转化项目(编号:202304295107020019) Fund programs National Natural Science Foundation of China(No.82404970)Natural Science Research Project of Anhui Educational Committee(No.2023AH053170)Clinical Medical Research Translational Project of Anhui Province(No.202304295107020019)
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