NRF2是调控细胞氧化应激反应的转录因子，NRF2抑制剂的开发也成为了肿瘤治疗领域的研究热点。除转录激活功能外，NRF2可与RPA1相互作用，通过ARE-NRE元件对某些基因（例如：MYLK）发挥转录抑制作用。前期实验表明：抑癌因子FOCAD基因的启动子中，存在ARE-NRE样序列，而且NRF2、RPA1和sMAF均可与该序列相结合，并发挥调控作用，所以NRF2 可能对FOCAD基因的具有转录负调控功能。本课题主要以非小细胞肺癌（NSCLC）为模型，分析NRF2和FOCAD在NSCLC组织和细胞中的表达关系；通过NRF2基因敲除或过表达的方法，明确NRF2对FOCAD基因的靶向负调控作用，并分析RPA1与sMAF在FOCAD基因ARE-NRE模型中的竞争关系；同时，通过体内外检测，评价NRF2抑制剂在抑癌过程中对FOCAD的依赖性及机制，为以NRF2抑制剂为基础的肿瘤治疗提供新的研究思路。

NRF2 is a transcription factor, which regulates oxidative stress response, and the development of NRF2 inhibitor has been the central issue in the field of cancer therapy. Besides transcriptional activation, NRF2 can inhibit the transcription of some genes (eg. MYLK) through RPA1 and .ARE-NRE sequence. Our previous results indicated that FOCAD promoter contains ARE-NRE-like sequence. All of NRF2, RPA1 and sMAF could bind to the sequence and regulate the transcription of FOCAD, suggesting that NRF2 may regulate FOCAD transcription negatively. In this project, the expression relationship between NRF2 and FOCAD will be analyzed in non-small cell lung cancer (NSCLC) tissue and cell line models. The negative regulation of NRF2 on FOCAD will be confirmed via NRF2 knockout and overexpression in NSCLC cells, and the competitive binding relationship between RPA1 and sMAF will be analyzed using ARE-NRE in FOCAD promoter. In addition, the dependence of FOCAD and related mechanism in the anti-cancer function of NRF2 inhibitor will be investigated in vitro and in vivo, providing a novel research insight for the cancer therapy based on NRF2 inhibitor.