一种新型内源性多肽PDAEP调控子宫内膜癌恶性进展的作用与机制研究

PDAEP是我们借助多肽组学筛选获得的一条功能未知、在子宫内膜癌（EC）组织中差异低表达的内源性多肽。前期研究发现，PDAEP可以抑制EC细胞的增殖和侵袭迁移，促进细胞凋亡；动物实验显示，PDAEP可以抑制肿瘤的生长和侵袭转移；进一步转录组学分析和实验揭示PDAEP可能通过负调控NF-κB信号通路发挥抗EC作用。本研究拟通过临床样本分析PDAEP在不同期别EC组织的表达规律，揭示其与EC恶性进展的相关性；通过体外实验明确PDAEP对不同EC细胞系增殖、凋亡和侵袭转移的影响；通过pull-down等实验寻找其作用靶蛋白，并以NF-κB信号通路为线索，系统阐明PDAEP作用的分子机制；通过动物实验，论证PDAEP对EC发展和侵袭转移的影响与机制，系统论证PDAEP治疗EC的可能性；从化学修饰角度出发，寻找提高PDAEP稳定性与活性的方法。研究若获成功，有望为EC的治疗提供新选择。

PDAEP, an endogenous polypeptide identified by mass spectrometry, is differentially lower expressed in human endometrial cancer tissue and its function remains unknown. Our primary results showed PDAEP can inhibit EC cell proliferation and migration, and promote cell apoptosis in vitro and can suppress tumor growth and metastasis in vivo by down-regulation NF-κB signaling pathway, presenting the potential therapeutic effect on EC. This study aims to analyze the expression and the role of PDAEP in human endometrial cancer. Therefore, a series of in vitro experiments, i.e. proliferation, migration, apoptosis assay and in vivo tests, i.e. xenograft model and metastasis model are both included to verify the possibility and feasibility of PDAEP targeting EC progression. Pull down experiments followed by Rescue experiments will be performed respectively to demonstrate the complete profile for EC progression by which PDAEP is involved. Chemical modifications, through which the stability and activity are improved for PDAEP are also considered in these experiments. Overall, this study will provide a new strategy for EC treatment.