我国前列腺癌的发病率及死亡率逐年上升，前列腺癌尤其是去势抵抗性前列腺癌（CRPC）是临床治疗的难点。课题组前期发现膜泡蛋白COPB2在CRPC患者中显著高表达，干扰COPB2显著抑制CRPC细胞的增殖和侵袭并促进其凋亡。进一步发现PC-3细胞中COPB2抑制NUPR1的表达，两者在组织和细胞中的表达呈显著负相关。推测COPB2作为癌蛋白参与前列腺癌进程，与NUPR1互相调控在CRPC进展中发挥重要作用，为此，拟进行（1）检测临床标本COPB2及NUPR1的表达，评价其与CRPC进程及预后相关性；（2）采用体内外及功能回补实验证实COPB2与NUPR1互相调控对前列腺癌增殖和侵袭的影响；（3）探究COPB2与NUPR1在CRPC中互相调控激活/抑制的关键下游信号。本研究通过阐明COPB2与NUPR1在CRPC中互相调控的作用机制，有望为诊断前列腺癌提供新指标，为开发有效药物提供新依据。

The incidence and mortality of prostate cancer in our country has been increasing. Prostate cancer, especially castration-resistant prostate cancer (CRPC), is a difficult about clinical treatment. Based on our previous studies, the membrane vesicle COPB2 indicated significant higher expression in CRPC patients. Interference with COPB2 can inhibit the proliferation, invasion of CRPC cells and promote its apoptosis. Furthermore, COPB2 inhibited the expression of NUPR1 in PC-3 cells, the expression of COPB2 and NUPR1 was negatively correlated with each other both in tissues and cells. It is presumed that COPB2 participates in the prostate cancer process as an oncoprotein, and plays an important role in the progress of CRPC through mutual regulating NUPR1. To further study: (1) to test the expression of COPB2 and NUPR1 in tissue and assess their correlation with the clinical prognosis of CRPC patients; (2) interaction for COPB2 and NUPR1 to regulate the proliferation and invasion of prostate cancer in vivo, vitro and rescue experiments; (3) to explore the key downstream signals of COPB2 and NUPR1 in CRPC. By clarifying the mechanism of the interaction between COPB2 and NUPR1 in CRPC, our present study will provide new markers for the diagnosis of prostate cancer, and a basis for the development of effective drugs.