RNA剪接和加工是真核细胞基因表达的一个重要生物过程，RNA剪接异常所产生的基因也是引起各类疾病，尤其是癌症的重要来源。因此研究肿瘤中RNA剪接调控对于探索肿瘤病因以及癌症的预防和治疗具有重要意义。NRF2信号通路是机体内重要的抗氧化防御系统，在癌症的化学预防中发挥重要作用。但在许多肿瘤中，由于KEAP1基因或NRF2基因等突变导致NRF2在肿瘤细胞内呈高表达，促进肿瘤细胞恶性增殖以及耐药性，目前尚未见NRF2调控RNA剪接的研究报道。基于实验室前期结果，我们假设肿瘤细胞内NRF2调控RNA剪接机制：（１）NRF2促进剪接体组装蛋白Smn的转录水平以及Smn复合体的蛋白水平影响剪接体的剪接功能；（２）NRF2能够与Smn复合体直接结合并共定位在剪接体加工场所-卡哈尔体内参与RNA剪接。本项目将为进一步明确Nrf2病理和生理功能及生物学意义打下基础, 为肿瘤治疗提供新思路和新靶点。

RNA splicing is an important biological process of gene expression and regulation in eukaryotic cells, but the aberrant isoforms of genes caused by RNA splicing was associated with many diseases, especially cancer. Understanding the RNA splicing in cancer offers new revenues for cancer prevention and therapy. NRF2 (Nuclear factor erythroid 2-related factor 2, also called NFE2L2) is activated by oxidative stress and electrophiles. In normal cells, production of antioxidant proteins through the stabilization of NRF2 is central to defense against oxidative stress, and for maintaining redox homeostasis in cells. In contrast, cancer cells frequently have mutations in NRF2/or KEAP1 gene that result in the stabilization and constitutive activation of the NRF2 protein. The role of NRF2 in regulating RNA splicing is still unknown. Based on our preliminary RNA-seq data in A549 cells, we hypothesize that in cancer cells the molecular mechanism of NRF2 in regulating RNA splicing may involve: (1) up-regulation of the Smn gene expression and the expression levels of Smn complexes; (2) and through direct interaction with　Smn complex in Gems and Cajal bodys. Our study has therapeutic implications as it suggested that cellular processes (like splicing) and some of the spliced genes may provide targets for anti-cancer therapies.