环状RNA参与肿瘤的发生发展，但其在化学致癌中的具体机制尚不清楚。我们前期发现4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁酮（NNK）染毒导致circPRMT10低表达，且circPRMT10低表达促进肺癌细胞的迁移，提示circPRMT10在NNK致肺癌中具有潜在功能。进一步预实验发现NNK能够诱导RNA结合蛋白QKI启动子区高甲基化并下调QKI蛋白表达，提示QKI与circPRMT10异常表达有关。据此，我们提出假设：NNK通过诱导QKI甲基化而下调QKI蛋白，进而调控circPRMT10的生成，促进肺癌发生。本课题拟采用慢病毒稳转细胞构建、裸鼠成瘤、去甲基化处理等方法，探讨circPRMT10在NNK诱导肺癌发生中的具体功能及NNK通过甲基化修饰影响circPRMT10环化生成的内在机制。进一步揭示NNK诱发肺癌的病因学机制，为烟草有关肺癌治疗靶点的寻找提供新的线索和科学依据。

Circular RNAs play a vital role in cancer occurrence and development. However, our knowledge about the mechanisms of circular RNAs on the chemical carcinogenesis is currently limited. Previously, we have found the expression of circPRMT10 was reduced in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced cells, and its downregulation promoted the migration of lung cancer cells, suggesting the potential functions of circPRMT10 in NNK-induced lung tumorigenesis. Further experiments revealed that the level of RNA-binding protein QKI was repressed due to the hypermethylation of QKI promoter region induced by NNK stimulation, suggesting that QKI was involved in the circularization of circPRMT10. Based on these previous results, we hypothesized that NNK stimulation led to the hypermethylation of QKI promoter region, which caused the epigenetic repression of QKI protein and thus inhibited the production of circPRMT10. And finally, downregulation of circPRMT10 promoted lung carcinogenesis induced by tobacco-related carcinogen NNK. In this project, lentiviral-transfected cells, nude mouse tumorigenicity assay and demethylation treatment were used to elucidate the functions of circPRMT10 in NNK-induced lung cancer and its mechanisms of circularization regulated by NNK-caused methylated modification of QKI. Totally, our results will further reveal the etiology of lung cancer induced by NNK and then provide new clues and lay a foundation for further research of therapeutic targets in tobacco-related lung cancer.