核小体结合蛋白（NSBP1）又名HMGN5，是高迁移族核小体结合蛋白家族成员，通过与组蛋白H1竞争结合核小体对染色质重塑调节发挥重要的作用。本课题组在早期研究中首次发现NSBP1在前列腺癌组织中高表达，并在后续系列研究中证实NSBP1具有很强的促进前列腺癌细胞增殖浸润和抑制凋亡的作用，且近期研究发现NSBP1在前列腺癌细胞中的表达情况与癌细胞对放化疗敏感性相关，具有很高的临床应用价值。然而NSBP1在前列腺癌中高表达的调控机制尚不清楚，这严重阻碍了以NSBP1为靶点的前列腺癌治疗转化研究。本项目拟通过CRISPR技术筛查NSBP1启动子区中的关键顺式作用元件，进而通过分子生物学手段解析NSBP1在前列腺癌中高表达的转录调控机制，并在此基础上通过对NSBP1调控元件予以干预进行临床转化研究。

Nucleosomal binding protein 1 (NSBP1), also known as HMGN5, is a member of high-mobility group nucleosome binding domain (HMGN) family. NSBP1 plays an important role in chromatin remodeling by competing with histone H1 to binding on nucleosome. NSBP1 is overexpressed in prostate cancer tissue, which was identified by our group in 2001, and our latter investigation proved that NSBP1 is involved in promoting prostate cancer cells proliferation, anti-apoptosis and invasion. The latest studies shows that the expression of NSBP1 relates to radiotherapy insensitivity of prostate cancer cells, suggesting the high clinical application value of NSBP1. Nevertheless, the mechanism through which NSBP1 is upregulated in prostate cancer is still unknown, and it heavily hinders the research on applying NSBP1 into prostate cancer treatments. This project aims at identifying the key cis-acting element in the promoter of NSBP1 by CRISPR/Cas9 system, and determining how NSBP1 is upregulated in prostate cancer by molecular biological techniques. Further, we will assess the potential value of NSBP1 on prostate cancer treatment through interfering the key cis-acting element. The accomplishment of this project will provide a theoretical basis for personalized therapy on prostate cancer.