分子靶向药用于多种恶性肿瘤的治疗，但针对口腔鳞癌(OSCC)分子靶向新疗法的发展远滞后于其它癌症。锌指蛋白750（ZNF750）是头颈部鳞癌中唯一所知位于局灶性缺失的基因，是启动细胞分化的关键。预实验发现OSCC组织及细胞中ZNF750降低或缺失、组织中细胞周期转录激活因子E2F2增多；过表达ZNF750可上调OSCC细胞分化基因并下调E2F2表达、阻滞细胞周期进程与细胞增殖等，推测ZNF750功能缺失可使细胞分化受损，对调控细胞周期G1/S检测点的E2F2抑制减弱，导致OSCC细胞增殖。本课题拟研究ZNF750的功能状态在OSCC恶性进展中的意义及生物学功能，确定ZNF750调控E2F2转录活性的顺式作用元件，并明确ZNF750调控E2F2的关键分子功能区及招募的辅助因子，揭示ZNF750抑制口腔鳞癌恶性进展的分子机制，为OSCC治疗及研发以ZNF750为靶点的分子靶向药奠定基础。

Molecularly targeted drugs are used in the treatment of a variety of malignant tumors, but this approach to developing novel therapies for oral squamous cell carcinoma (OSCC) has lagged behind the progress seen for other cancers. ZNF750 is the only known gene residing in focal deletion in head and neck squamous cancers, and is key factor to turn on the terminal epidermal differentiation gene program. Our preliminary studies showed that ZNF750 expression was decreased or deleted in the OSCC tissues and cells. The expression of the E2F2 was increased in OSCC tissues. Over-expression of ZNF750 up-regulated the expression of differentiation genes but down-regulated E2F2 expression, blocked the cell cycle progression and cell proliferation. The present studies indicated that the loss of function of ZNF750 resulted in the cell differentiation damage, reduced the E2F2 expression which regulated the cell cycle G1/S check point, leading to OSCC cells proliferation. The present study is to explore the function of ZNF750 in OSCC malignant progression and its biological function, identification of the E2F2 transcriptional activity Cis-elements regulated by ZNF750, and confirming the key molecular functional domain of ZNF750 and the recruitment cofactor by ZNF750 for regulation the E2F2, to reveal the molecular mechanisms of ZNF750 for inhibiting oral squamous cell carcinoma malignant progression. This study will provide a theoretical foundation for treatment of OSCC and develope the molecularly targeted drugs upon ZNF750.