Feng Yanyan, Sun Chuanyu, Zhang Lifeng, Wan Hongyuan, Zhou Hangsheng, Chen Yongquan, Zhu Lijie, Xia Guowei, Mi Yuanyuan
Wuxi Medical College, Jiangnan University, Wuxi, China.
Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi, China.
Front Oncol. 2022 May 6;12:865317. doi: 10.3389/fonc.2022.865317. eCollection 2022.
There is increasing evidence that coatomer protein complex subunit beta 2 (COPB2) plays an important role in various cancer types. This study explored the role and the downstream mediators of in prostate cancer (PCa). The expression of COPB2 was determined by the Cancer Genome Atlas database and enzyme-linked immunosorbent assay. COPB2 expression was upregulated in PCa tissues and correlated with Gleason score, biochemical recurrence, and poor prognosis. The functional roles of in PCa were verified through a series of experiments. Knocking down COPB2 expression inhibited the growth and clonogenesis of PCa cells, promoted cell apoptosis, and inhibited the ability of scratch repair, invasion of PCa cells, and tumor growth in Nude mice. To analyze downstream signaling pathways, ingenuity pathway analysis, GSEA, and whole-genome expression spectrum GeneChip analysis were used. Western blot revealed that COPB2 expression promoted the proliferation and invasion of PCa cells by regulating the MAPK/TGF-β signaling pathway. The interacting protein (nuclear protein 1, NUPR1) was identified Co-IP, real-time PCR, Western blot, and TCGA database in sampled tissues. The expressions of the interaction proteins NUPR1 and COPB2 were negatively regulated by each other. could be a new biomarker for PCa diagnosis and monitoring and to provide a theoretical basis for identifying effective drug intervention targets through in-depth mechanistic studies.
越来越多的证据表明，外套膜蛋白复合物亚基β2（COPB2）在多种癌症类型中发挥重要作用。本研究探讨了COPB2在前列腺癌（PCa）中的作用及其下游介质。通过癌症基因组图谱数据库和酶联免疫吸附测定法测定COPB2的表达。COPB2在PCa组织中表达上调，并与Gleason评分、生化复发和不良预后相关。通过一系列实验验证了COPB2在PCa中的功能作用。敲低COPB2表达可抑制PCa细胞的生长和克隆形成，促进细胞凋亡，并抑制划痕修复能力、PCa细胞侵袭及裸鼠体内肿瘤生长。为分析下游信号通路，采用了 Ingenuity 通路分析、基因集富集分析（GSEA）和全基因组表达谱基因芯片分析。蛋白质印迹法显示，COPB2表达通过调节 MAPK/TGF-β信号通路促进PCa细胞的增殖和侵袭。通过免疫共沉淀、实时定量聚合酶链反应、蛋白质印迹法和肿瘤基因组图谱（TCGA）数据库在采样组织中鉴定出相互作用蛋白（核蛋白1，NUPR1）。相互作用蛋白NUPR1和COPB2的表达相互负调控。COPB2可能成为PCa诊断和监测的新生物标志物，并为通过深入的机制研究确定有效的药物干预靶点提供理论依据。
