研究表明多环芳烃（PAHs）暴露可增加肺癌发病率，明确其致癌机制对肺癌防控至关重要。我们前期研究发现TRIM36基因启动子在PAHs诱导细胞恶性转化过程中发生高甲基化并下调基因表达。另外，TRIM36在肺癌中低表达并与肺癌预后相关，且其高表达肺癌细胞株生长变慢，提示TRIM36基因高甲基化在PAHs致癌过程有重要作用。本研究拟利用PAHs暴露人群和肺癌组织分析TRIM36基因甲基化和表达与PAHs暴露和肺癌的关系；构建TRIM36高表达/干扰细胞株研究TRIM36对PAHs诱导的DNA损伤修复，细胞恶性转化等生物学功能的影响；通过蛋白免疫沉淀、液相色谱-质谱分析和泛素化/SUMO化实验，鉴定TRIM36的作用底物并进行相关功能分析。本研究可进一步完善PAHs致癌的表观遗传调控机制，为发掘新的PAHs致癌早期监测生物标志和治疗靶点提供依据。

It is proved that long term exposure of polycyclic aromatic hydrocarbons (PAHs) can increase the incidence of lung cancer, and understanding its carcinogenic mechanism is vital for lung cancer preventation. Our previous data showed that the gene promoter of tripartite motif containing family 36 (TRIM36) is hypermethylated during PAHs induced human bronchial epithelial cell transformation and its gene expression is also repressed. Further study suggested that the expression of TRIM36 is down-regulated in human lung cancer and correlated to prognosis of lung cancer patients. Over-expression of TRIM36 could delay the growth of lung cancer cell lines. Our previous data suggests that hypermethylation of TRIM36 plays important roles in PAHs carcinogenesis. In this study, we plan to explore the correlation of TRIM36 gene hypermethylation and expression with PAHs exposure and lung cancer by studying the PAHs exposed population and examining the lung cancer tissues. In addition, we will construct TRIM36 overexpression and knock down cell lines to study the function of TRIM36 in carcinogenic effects induced by PAHs, such as DNA damage repair, cell transformation and etc. Finally, we intend to reveal the mechanism of TRIM36 function by identifying its substrates, using protein immunoprecipitation, combined with LC-MC and ubiquitination/sumoylation assay. This study will shed light on the epigenetic mechanisms of PAHs carcinogenesis and will provide theoretical basis for searching novel biomarkers and new targets for the early detection and therapy of PAHs induced lung cancer.