hOGG1基因表观调控异常在非小细胞肺癌中作用及机制研究

肺癌是世界范围内发病率和死亡率极高的恶性肿瘤之一。hOGG1是一种DNA修复酶，可以从DNA切除修复8-羟基鸟嘌呤。研究表明该基因变异可能会影响个体修复损伤DNA的能力，促进肺癌的发生。我们前期工作证实hOGG1基因甲基化与非小细胞肺癌 (NSCLC) 相关 (Lung Cancer,2008; J Thorac Oncol,2010)，进一步实验得出hOGG1基因甲基化异常可能是其mRNA下调的主要原因。因此提出假设：hOGG1基因特定区域表观调控异常可能影响了转录因子的结合，是导致其表达异常的主要原因。本项目拟以细胞株和外周血PBMC为材料，运用RFLP，MSP，EMSA，ChIP等技术，探索hOGG1基因变异与NSCLC发生发展的关系，明确可能导致hOGG1表达异常的表观修饰机制，阐明hOGG1基因表观遗传调控机制在NSCLC发生、发展中的作用，为临床诊断、预防及治疗提供新的思路。

Lung cancer is one of the malignant tumors worldwidely, which has high morbidity and mortality. hOGG1 is a DNA repair enzyme, which can repair damaged DNA by specifically excising 8-dihydro-8-8oxoguanine (8-OH-G). Studies have shown that gene variation may affect the ability of the repair of damaged DNA individually, and promote the initiation of lung cancer. Our previous work confirmed that the hOGG1 gene methylation is associated with non-small cell lung cancer (NSCLC) (Lung Cancer, 2008; J Thorac Oncol, 2010). Further pre-preliminary experimental results found that the methylation status of hOGG1 might be an important factor in mRNA down-regulation of hOGG1. Therefore, the hypothesis was proposed: abnormal epigenetic modification of a specific region of hOGG1 gene may affect transcription factor binding, which is the main reason leads to abnormal expression. This project select cell lines and Peripheral blood mononuclear cell(PBMC) specimens as experimental material, using RFLP, MSP, EASA, ChIP methods, explore the relation between hOGG1 gene mutation and the initiation and development of NSCLC, may designate the potential epigenetic modification mechanism which results in hOGG1 abnormal expression, and clarify the role of the epigenetic regulation mechanisms of hOGG1 gene contribute to the initiation and development of NSCLC, provide new ideas for clinical diagnosis, prevention and treatment.