我们前期研究发现NUCB2的表达在前列腺癌(PCa)进展乃至去势抵抗性PCa(CRPC)转变过程中逐步上调，提示其在PCa进展过程中发挥重要的作用。前期预实验提示NUCB2可与LAPTM4B、SPAG5及AR发生相互作用，并能够调控LAPTM4B、SPAG5及AR的表达水平。乏氧是PCa生长的重要微环境，预实验发现乏氧可上调NUCB2、LAPTM4B、SPAG5和AR的表达，且NUCB2存在HIF-1α的潜在结合部位。我们有理由推测，NUCB2是受HIF-1α调控的靶基因并参与了PCa进展的调节，乏氧可上调NUCB2、LAPTM4B、SPAG5和AR的表达，并且增强它们之间的相互作用，规避雄激素剥夺治疗引起的不良生存环境的影响，使细胞免于凋亡，协同促进PCa的进展和恶化，提高PCa中CRPC相关信号通路对乏氧和极低浓度雄激素刺激的反应敏感性，朝着有利于细胞生长进而进展为CRPC的方向转变。

Prvious research indicated that that NUCB2 expression level is drastically increased in primary prostate cancer (PCa) relative to normal samples, metastatic PCa relative to primary PCa, and castrate-resistant PCa (CRPC) relative to hormone naïve PCa, suggesting that NUCB2 can play an important role in CRPC progression. However, its expression regulation mechanism has not been elucidated. Hypoxia is one important microenvironment feature of PCa. Our previous studies indicated that NUCB2 can interact with LAPTM4B, AR and SPAG5 proteins. Our previous studies also indicated that HIF-1αmay bind to the NUCB2 promoter and can promote the expression of NUCB2, LAPTM4B, AR, and SPAG5 under hypoxia suggesting NUCB2 may sensitize the activity of CRPC pathway．Hypersensitivity of CRPC related pathways to the presence of androgen or hypoxic conditions in the cancer microenvironment，leading to enhanced cell survival and a CRPC-like phenotype. NUCB2 overexpression sensitizes PCa cells to the related signal pathways in response to androgen stimulation at a very low level after COCl2-induced hypoxia stimulation．These data imply that increased NUCB2 levels protect androgen-dependent PCa cells from the treatment stress induced by androgen withdrawal and facilitate CRPC transition after castration．