靶向前列腺癌干细胞是根治侵袭性前列腺癌（PCa）的前瞻性策略，需要筛选鉴定相关分子标志物/驱动基因。我们通过TCGA数据库筛选出伴侣蛋白NACB，其在PCa等多种肿瘤中异常上调，但分子机制不明。前期结果显示，NACB在PCa组织的表达与Gleason评分呈正相关，并提示预后不良；NACB可促进PCa细胞的增殖/迁移/成球等干细胞样表型，该效应可能通过上调干细胞关键因子BMI-1介导；NACB过表达可能与海绵分子lncRNA AGAP2-AS1/miR-15a失调相关。本课题拟继续深入研究：①NACB作为干细胞关键性调控因子诱导PCa干性表型的生物学功能；②NACB靶向BMI-1的分子机制和AGAP2-AS1→miR-15a→NACB→BMI-1调控轴的存在；③通过大样本PCa人群临床病理分析评价NACB作为PCa分层诊断标志物的价值。本项目将为侵袭性PCa的精准诊疗提供有意义的研究资料。

Targeting prostate cancer stem cells is a prospective strategy for the radical cure of aggressive prostate cancer (PCa), which requires screening and identifying related molecular markers/drive genes. We screened out the chaperone protein NACB from the TCGA database. NACB is abnormally up-regulated in various tumors including PCa, but the underlying molecular mechanisms are unknown. Preliminary results showed that the expression of NACB in PCa tissues was positively correlated with Gleason score and suggested poor prognosis; NACB could promote stem cell-like phenotype of PCa cells such as proliferation/metastasis/sphere formation, which may be mediated by up-regulating stem cell key factor BMI-1; NACB overexpression may be associated with dysregulation of the sponge molecules lncRNA AGAP2-AS1/miR-15a. This project is intended to continue studying in depth: (1) the biological functions of NACB that induces the stemness phenotype of PCa cells as a key regulator of stem cells; (2) molecular mechanisms of NACB targeting BMI-1, and AGAP2-AS1→miR-15a→NACB→BMI-1 regulatory axis; (3) evaluate the value of NACB as a stratified diagnostic marker for PCa by clinical pathological analysis of large sample PCa population. This project will provide significant research data for the precise diagnosis and treatment of aggressive PCa.