去势抵抗性前列腺癌（CRPC）是前列腺癌（PCa）治疗的难点。我们首次发现TXNDC5可促进CRPC的转变，但尚未明确调控其表达及功能的机制。PADI2通过将蛋白的精氨酸催化为瓜氨酸，参与肿瘤病变，但至今没有与PCa的研究报道。最近我们发现PADI2可瓜氨酸修饰TXNDC5蛋白并调控其表达；PADI2的表达在CRPC组织和长期雄激素剥夺培养后的PCa细胞中均显著升高；TXNDC5可与PADI2蛋白结合。在此基础上我们提出“PADI2通过瓜氨酸作用调控TXNDC5，并促进CRPC转变”的科学假说。本课题拟阐明PADI2对TXNDC5表达和功能的调控作用及其机制；探讨PADI2在CRPC病变中的功能及与雄激素受体通路的关系；研究TXNDC5对PADI2活性的影响；明确PADI2在PCa中表达的病理学特征。本课题的开展可望揭示新的CRPC调控机制，为寻找新的CRPC治疗药物提供理论及实验依据。

Castration-resistant prostate cancer (CRPC) has an extremely poor prognosis and remains a significant clinical challenge as the underlying mechanisms are largely unknown. Previously, our group has reported that TXNDC5 could promote CRPC progression through activating the androgen receptor pathway, but the mechanism regulating its expression and activity is still obscure. Peptidylarginine deiminase 2 (PADI2) could promote tumor progression through post-translationally modifying arginine into citrulline. However, to date, no detailed study has been reported between PADI2 and PCa. Recently, we found that 1) TXNDC5 protein was citrullinated by PADI2 and its expression could be regulated by PADI2 as well; 2) the PADI2 expression increased significantly in both CRPC tissues and PCa cells when placed under long-term androgen-deprivation condition; 3) TXNDC5 could bind with PADI2. Based on the above data, we hypothesized that “PADI2 could regulate the expression and function of TXNDC5 through citrullination and promote the progression of CRPC ”. Our subject is intended to: (1) elucidate the regulation and mechanism of PADI2 on the expression and function of TXNDC5; (2) determine the biological functions of PADI2 in CRPC and interactions between PADI2 and androgen-AR signaling pathway in vitro and in vivo; (3) study the effect of TXNDC5 on the biological activity of PADI2; (4) characterize the clinico-pathological features of PADI2. This study may reveal a novel regulative mechanism regarding CRPC and provide credible evidence to search for new treatment medicine.