CBX4在前列腺癌中的表达及意义

Expression of CBX4 in Prostate Cancer and Its Significance

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。

Objective:To investigate the expression of CBX4 in prostate cancer,the effect of CBX4 on ferroptosis in prostate cancer cells,and their significance.Methods:Oncomine,UALCAN and Human Protein Atlas(HPA)databases were used to analyze the differential expression of CBX4 in prostate cancer,the relationship between CBX4 expression and clinicopathological parameters of prostate cancer,and CBX4 expression and the survival of prostate cancer patients.The interaction between CBX4 gene and proteins was analyzed through String database.Furthermore,the protein level of CBX4 was detected by immunohistochemistry in prostate cancer tissue chips,and quantitative PCR was used to determine the mRNA level of CBX4 in different prostate cancer cells.We silenced CBX4 in prostate cells and evaluated the ferroptosis in prostate cancer cells by transmission electron microscopy,and the mRNA level of SLC7A11 was examined.Results:The data from Oncomine showed that the expression of CBX4 mRNA in prostate cancer tissue was significantly higher than that in normal tissue(P<0.001),which was further confirmed by Meta-analysis,and by data from HPA and UALCAN databases(P<0.05).Meanwhile,immunohistochemical and cellular assays confirmed the abnormally high expression of CBX4 in prostate cancer(P<0.05).The UALCAN analysis showed that CBX4 expression was positively correlated to the Gleason score and lymph node metastasis of prostate cancer(P<0.05),and the survival of patients in the high CBX4 expression group was obviously shorter than that in the low expression group(P<0.05).String results showed that CBX4 might interact with E3 ubiquitin protein ligases(RING2,RING1),polycomb rekaryotic protein(BMI-1)and DNA methyltransferase(DNMT3A).Moreover,interference in the CBX4 expression can promote ferroptosis of prostate cancer cells and inhibit the expression of SLC7A11.Conclusion:Data based on cellular and biological database showed that CBX4,involved in ferroptosis,is highly expressed in prostate cancer tissue,and its expression level is negatively correlated to the overall survival of prostate cancer patients,which indicates that CBX4,participating in the development of prostate cancer,may be a biomarker for prostate cancer outcomes and an important target for the diagnosis and treatment.