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
Gastric cancer(GC)is one of the most common malignancies,with an everincreasing incidence and high mortality rate.Chromobox4(CBX4),also named hPC2,is a small ubiquitin-related modifier(SUMO)E3 ligase.Previous studies ...Gastric cancer(GC)is one of the most common malignancies,with an everincreasing incidence and high mortality rate.Chromobox4(CBX4),also named hPC2,is a small ubiquitin-related modifier(SUMO)E3 ligase.Previous studies have found that high CBX4 expression is associated with tumor size,pathologic differentiation and decreased patient survival in hepatocellular carcinoma(HCC).However,the expression and prognostic value of CBX4 in GC have not been clarified.In our study,ONCOMINE,UALCAN,KaplanMeier Plotter,cBioPortal,DAVID 6.8 and TIMER were utilized.RT-PCR,immunohistochemistry(IHC),Western blot,CCK-8 assay,cell apoptosis assay,cell cycle assay were used to further verify in GC tissue samples or cell line.The transcriptional and protein level of CBX4 in GC tissues was found significantly elevated and a significant association between the expression of CBX4 and clinicopathological parameters was found in GC patients.Low expression of CBX4 in GC patients were correlated with a significantly improved prognosis.The functions of CBX4 are primarily related to the stem cell pluripotency signaling pathway,Hippo signaling pathway,HTLV-I infection,Notch signaling pathway,and N-glycan biosynthesis.Our results may provide novel insights for the selection of therapeutic targets and prognostic biomarkers for GC.展开更多
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。
基金This project was supported by the National Natural Science Foundation of China[grant number 81972655]the Program for Young Eastern Scholars at the Shanghai Institutions of Higher Learning[grant number QD2016004]+1 种基金the Shanghai Science and Technology Commission Research Project[grant number 14441903103]Shanghai Municipal Key Clinic Specialty.
文摘Gastric cancer(GC)is one of the most common malignancies,with an everincreasing incidence and high mortality rate.Chromobox4(CBX4),also named hPC2,is a small ubiquitin-related modifier(SUMO)E3 ligase.Previous studies have found that high CBX4 expression is associated with tumor size,pathologic differentiation and decreased patient survival in hepatocellular carcinoma(HCC).However,the expression and prognostic value of CBX4 in GC have not been clarified.In our study,ONCOMINE,UALCAN,KaplanMeier Plotter,cBioPortal,DAVID 6.8 and TIMER were utilized.RT-PCR,immunohistochemistry(IHC),Western blot,CCK-8 assay,cell apoptosis assay,cell cycle assay were used to further verify in GC tissue samples or cell line.The transcriptional and protein level of CBX4 in GC tissues was found significantly elevated and a significant association between the expression of CBX4 and clinicopathological parameters was found in GC patients.Low expression of CBX4 in GC patients were correlated with a significantly improved prognosis.The functions of CBX4 are primarily related to the stem cell pluripotency signaling pathway,Hippo signaling pathway,HTLV-I infection,Notch signaling pathway,and N-glycan biosynthesis.Our results may provide novel insights for the selection of therapeutic targets and prognostic biomarkers for GC.
