环氧合酶COX-2高表达是肺癌发生发展的风向指标，发现新型的肿瘤特异性COX-2表达调控因子意义重大。前期研究中，我们利用BSBP垂钓技术和蛋白质组学方法，在肺癌细胞中垂钓和确定了一个新型的COX-2启动子DNA 结合蛋白NMI，并证实其在肺癌细胞和组织中高表达、可调控COX-2转录和肺癌细胞生长，但NMI如何调控COX-2继而影响肺癌发生发展的分子机制及其临床意义，目前尚不清楚。本项目拟在肺癌细胞和动物模型中敲低或过表达NMI，研究其对COX-2表达、启动子活性和PGE2产生的调控以及对肿瘤生长的影响，揭示NMI/COX-2信号通路在肺癌发生发展中的作用和分子机制；并利用组织芯片，结合临床资料，分析肺癌患者组织中NMI/COX-2的表达水平及两者表达的相关性，并评估其与肺癌发生、分期、复发、预后的关系，明确其临床意义。本项目将为确立NMI 作为肺癌治疗新靶点提供理论和实验依据。

The high expression of COX-2 is the hallmarker of lung tumorigenesis. It is of important significant to discover the novel and tumor-specific factors which regulate COX-2 expression. In our preliminary study, we pulled down and identified NMI as a new COX-2 promoter-binding protein in lung cancer cells by BSBP（biotin-strepatavidin-beads pulldown）and proteomics techniques. We also showed that NMI was highly expressed in lung cancer cells and tumor tissues, regulated COX-2 transcription and lung cancer cell growth. However, so far it is unclear about the molecular mechanisms by which the NMI regulates COX-2 expression and lung tumorigenesis as well as its clinical implications. In this study, we will knockdown or overexpress NMI in human lung cancer cell lines and animal models, and then study the effects of NMI on COX-2 expression, promoter activity, PGE2 production, and tumor tumor cell growth, thereby revealing the mechanisms of action of the NMI/COX-2 signaling pathway in lung tumorigenesis. Moreover,we will use tissue array, combining with the clinical data, to analyze the expression levels and the correlation of NMI/COX-2 in tumor tissues from lung cancer patients, and to evaluate their relationship with lung tumorigenesis, pathological staging and patient prognosis, thereby identifying the clinical implications of NMI/COX-2. The results from this study will provide theoretical and experimental basis for the identification of the NMI/COX-2 signaling as a new therapeutic target for lung cancer treatment.