Objectives:Chromobox 4(CBX4),a polycomb protein family member linked to tumor pathogenesis via dysregulation,has an incompletely defined role in gastric cancer(GC).The study aimed to investigate the role and mechanism...Objectives:Chromobox 4(CBX4),a polycomb protein family member linked to tumor pathogenesis via dysregulation,has an incompletely defined role in gastric cancer(GC).The study aimed to investigate the role and mechanism of CBX4 in GC progression and evaluate its potential as a therapeutic target.Methods:CBX4 expression was assessed in GC tissues vs.adjacent non-cancerous tissues and in GC cell lines vs.normal gastric mucosal epithelial cells.Clinicopathological correlations were analyzed.Functional impacts of CBX4 were determined using knockdown and overexpression models in vitro(cell proliferation,migration,invasion)and in vivo(xenograft tumorigenesis in nude mice).Mechanistic studies evaluatedβ-catenin levels(total and nuclear)and transcriptional activity following CBX4 modulation.The functional dependency on Wnt/β-catenin signaling was tested using the pharmacological inhibitor XAV939 in CBX4-overexpressing cells.Results:CBX4 expression was significantly upregulated in GC tissues and cell lines.Elevated CBX4 levels strongly correlated with aggressive tumor characteristics,including larger tumor size,lymph node metastasis,and advanced Tumor,Node,Metastasis(TNM)stage.Functionally,CBX4 knockdown suppressed GC cell proliferation,migration,invasion in vitro,and tumorigenesis in vivo.Conversely,CBX4 overexpression enhanced these malignant traits.Mechanistically,CBX4 depletion reduced total and nuclearβ-catenin levels and inhibited its transcriptional activity,while CBX4 overexpression had the opposite effect.Critically,XAV939-mediated inhibition of Wnt/β-catenin signaling attenuated the oncogenic effects induced by CBX4 overexpression.Conclusion:CBX4 upregulation promotes GC progression viaβ-catenin signaling activation.The CBX4/β-catenin axis emerges as a promising therapeutic target,offering potential for the development of precision treatment strategies in GC management.展开更多
多梳蛋白家族(polycomb group proteins,PcG)是通过修饰染色质对靶基因进行转录抑制的表观遗传调控复合物。研究发现CBX4能介导与疾病发生的相关信号通路,从而参与增殖、分化及预后等生物学过程。该文就CBX4与肿瘤发生的相关机制及潜在...多梳蛋白家族(polycomb group proteins,PcG)是通过修饰染色质对靶基因进行转录抑制的表观遗传调控复合物。研究发现CBX4能介导与疾病发生的相关信号通路,从而参与增殖、分化及预后等生物学过程。该文就CBX4与肿瘤发生的相关机制及潜在的临床应用价值等方面的研究作一综述。展开更多
目的:探究CBX4在前列腺癌组织中的表达情况、对前列腺癌细胞铁死亡的影响以及临床意义。方法:利用Oncomine、UALCAN和Human Protein Atlas(HPA)数据库分析CBX4在前列腺癌组织与正常组织中的表达差异、CBX4表达与前列腺癌患者的临床病理...目的:探究CBX4在前列腺癌组织中的表达情况、对前列腺癌细胞铁死亡的影响以及临床意义。方法:利用Oncomine、UALCAN和Human Protein Atlas(HPA)数据库分析CBX4在前列腺癌组织与正常组织中的表达差异、CBX4表达与前列腺癌患者的临床病理参数的关系及其对患者生存期的影响,String数据库分析与CBX4相互作用的蛋白;通过免疫组织化学方法检测前列腺癌组织芯片中CBX4的表达情况,实时荧光定量PCR测定CBX4在不同前列腺癌细胞水平的表达;透射电镜评价干扰CBX4表达后前列腺癌细胞的铁死亡情况,实时荧光定量PCR检测铁死亡下游分子SLC7A11的表达变化。结果:Oncomine分析结果显示前列腺癌组织中CBX4 mRNA的表达较正常组织显著升高(P<0.001);Meta分析、HPA和UALCAN的结果进一步证实CBX4的mRNA和蛋白水平在前列腺癌组织中明显增高(P<0.05);免疫组织和细胞水平的实验结果证实CBX4在前列腺癌异常高表达(P<0.05);UALCAN分析发现CBX4的表达与前列腺癌的Gleason评分和淋巴结转移呈正相关(P<0.05)。同时,CBX4高表达组患者的生存期明显短于低表达组(P<0.05)。String分析的结果表明,CBX4可能与E3泛素蛋白连接酶RING2和RING1、多梳复核蛋白BMI-1及DNA甲基转移酶DNMT3A蛋白相互作用;干扰CBX4的表达,可促进前列腺癌细胞的铁死亡,且抑制铁死亡上游分子SLC7A11的表达变化。结论:基于生物信息和细胞水平的实验提示,CBX4在前列腺癌组织中异常高表达,可能参与了细胞的铁死亡,且其表达水平与前列腺癌患者总体生存周期呈负相关,表明CBX4可能为前列腺癌预后的生物学标志物,参与前列腺癌的发生发展,为重要的诊断和治疗靶点。展开更多
基金funded by the National Natural Science Foundation of China(Grant No.82473566)the Science and Technology Plan Project of Jiangsu Province(Grant No.BE2022728)+2 种基金the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(Grant No.24KJB320015)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(Grant Nos.SJCX24_1822 and SJCX21_1354)the Soochow University Open Topic from Jiangsu Engineering Laboratory of Novel Functional Polymeric Materials(Grant No.SDGC2312).
文摘Objectives:Chromobox 4(CBX4),a polycomb protein family member linked to tumor pathogenesis via dysregulation,has an incompletely defined role in gastric cancer(GC).The study aimed to investigate the role and mechanism of CBX4 in GC progression and evaluate its potential as a therapeutic target.Methods:CBX4 expression was assessed in GC tissues vs.adjacent non-cancerous tissues and in GC cell lines vs.normal gastric mucosal epithelial cells.Clinicopathological correlations were analyzed.Functional impacts of CBX4 were determined using knockdown and overexpression models in vitro(cell proliferation,migration,invasion)and in vivo(xenograft tumorigenesis in nude mice).Mechanistic studies evaluatedβ-catenin levels(total and nuclear)and transcriptional activity following CBX4 modulation.The functional dependency on Wnt/β-catenin signaling was tested using the pharmacological inhibitor XAV939 in CBX4-overexpressing cells.Results:CBX4 expression was significantly upregulated in GC tissues and cell lines.Elevated CBX4 levels strongly correlated with aggressive tumor characteristics,including larger tumor size,lymph node metastasis,and advanced Tumor,Node,Metastasis(TNM)stage.Functionally,CBX4 knockdown suppressed GC cell proliferation,migration,invasion in vitro,and tumorigenesis in vivo.Conversely,CBX4 overexpression enhanced these malignant traits.Mechanistically,CBX4 depletion reduced total and nuclearβ-catenin levels and inhibited its transcriptional activity,while CBX4 overexpression had the opposite effect.Critically,XAV939-mediated inhibition of Wnt/β-catenin signaling attenuated the oncogenic effects induced by CBX4 overexpression.Conclusion:CBX4 upregulation promotes GC progression viaβ-catenin signaling activation.The CBX4/β-catenin axis emerges as a promising therapeutic target,offering potential for the development of precision treatment strategies in GC management.
文摘目的:探究CBX4在前列腺癌组织中的表达情况、对前列腺癌细胞铁死亡的影响以及临床意义。方法:利用Oncomine、UALCAN和Human Protein Atlas(HPA)数据库分析CBX4在前列腺癌组织与正常组织中的表达差异、CBX4表达与前列腺癌患者的临床病理参数的关系及其对患者生存期的影响,String数据库分析与CBX4相互作用的蛋白;通过免疫组织化学方法检测前列腺癌组织芯片中CBX4的表达情况,实时荧光定量PCR测定CBX4在不同前列腺癌细胞水平的表达;透射电镜评价干扰CBX4表达后前列腺癌细胞的铁死亡情况,实时荧光定量PCR检测铁死亡下游分子SLC7A11的表达变化。结果:Oncomine分析结果显示前列腺癌组织中CBX4 mRNA的表达较正常组织显著升高(P<0.001);Meta分析、HPA和UALCAN的结果进一步证实CBX4的mRNA和蛋白水平在前列腺癌组织中明显增高(P<0.05);免疫组织和细胞水平的实验结果证实CBX4在前列腺癌异常高表达(P<0.05);UALCAN分析发现CBX4的表达与前列腺癌的Gleason评分和淋巴结转移呈正相关(P<0.05)。同时,CBX4高表达组患者的生存期明显短于低表达组(P<0.05)。String分析的结果表明,CBX4可能与E3泛素蛋白连接酶RING2和RING1、多梳复核蛋白BMI-1及DNA甲基转移酶DNMT3A蛋白相互作用;干扰CBX4的表达,可促进前列腺癌细胞的铁死亡,且抑制铁死亡上游分子SLC7A11的表达变化。结论:基于生物信息和细胞水平的实验提示,CBX4在前列腺癌组织中异常高表达,可能参与了细胞的铁死亡,且其表达水平与前列腺癌患者总体生存周期呈负相关,表明CBX4可能为前列腺癌预后的生物学标志物,参与前列腺癌的发生发展,为重要的诊断和治疗靶点。
文摘目的利用生物信息学技术分析CBX1在胃癌中的表达,探讨CBX1与胃瘤临床病理特征的相关性,阐明CBX1对胃瘤早期诊断和预后的影响。方法利用Oncomine数据库、GEPIA数据库分析CBX1在胃癌组织和正常胃组织中转录水平的表达差异;利用Western blot检测CBX1在正常胃黏膜细胞GES-1和胃癌细胞SGC7901中的蛋白表达差异;利用Human Protein Atlas网站分析CBX1在胃癌组织及正常胃组织中翻译水平的表达差异;利用UALCAN数据库及Kaplan Meier-Plotter在线分析工具,阐明CBX1高表达与胃癌患者病理参数及患者生存率之间的关系;利用GEPIA数据库寻找与CBX1有紧密作用关系的蛋白,利用STRING数据库,构建蛋白质互作(PPI)网络,Scytoscape软件对PPI可视化,并利用Metascape网站进行基因本体富集分析,Starbase网站进行京都基因与基因组百科全书通路富集分析。结果CBX1在胃瘤中高表达,且与胃瘤的肿瘤分级、分期相关;生存分析结果显示CBX1高表达与胃癌患者生存率密切相关;富集分析结果显示与CBX1相互作用的蛋白主要发挥组蛋白修饰、mRNA组装功能。结论CBX1在胃瘤中呈高表达,并与胃瘤多个病理性指标相关。
