基于增强子表观遗传调控的N-PAHs诱导肺癌肿瘤细胞侵袭转移研究

项目名称： 基于增强子表观遗传调控的N-PAHs诱导肺癌肿瘤细胞侵袭转移研究

项目编号： No.21677091

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 化学工业

项目作者： 云洋

作者单位： 山西大学

项目金额： 30万元

中文摘要： 室外空气污染被确定为人类一类致癌物。近期研究提示，PM2.5暴露可诱导人肺癌细胞A549的侵袭转移，二次有机气溶胶（SOA）最主要的组分硝基多环芳烃 （N-PAHs）因具有比其前体PAHs更强致突变和致癌作用而可能成为肺癌肿瘤癌变效应的重要贡献者。为此，本项目拟开展以下工作：（1）按照“癌细胞骨架系统损伤脱离周围癌细胞-裂解细胞基质侵入周围组织-黏附血管内皮炎性细胞-血行转移”的顺序，明确NPAHs对肺癌肿瘤侵袭转移级联效应的影响，解析N-PAHs内暴露机制。（2）阐明N-PAHs直接攻击Hippo-YAP信号通路，诱导肺癌肿瘤侵袭转移级联效应发生的细胞学基础。（3）分析TEAD-YAP转录因子驱动组蛋白修饰活化增强子直接开启癌基因高效转录的表观遗传控机制。旨在为N-PAHs人群暴露健康效应研究提供科学依据。

中文关键词： 硝基多环芳烃；肺癌；Hippo-YAP；增强子；组蛋白修饰

英文摘要： The outdoor air pollution is confirmed as carcinogenic to humans, and the airborne particulate mixture is most closely associated with increased cancer incidence, especially lung cancer. Previous studies have documented that PM2.5 promoting lung cancer cell metastasis, and NPAHs maybe the important contributor to the effect, because their stronger mutagenic and carcinogenic effects of than PAHs. However, existing research focused mainly on the carcinogenic toxicity of PAHs. It is absent of the experimental evidence about NPAHs promoting lung cancer cell metastasis studies. In the present study, 1）In order cytoskeleton damage - invasion surrounding cells adhesion of vascular endothelial inflammatory cells - cancer transfer through blood, we will analyse the effects of NPAHs on lung cancer cell metastasis and determined the internal exposure mechanism of the NPAHs. 2） explore mechanisms of NPAHs exposure directly inhibit the “Hippo-YAP” on the early tumor metastasis and caner development. 3）illuminate mechanism of Enhancer regulation epigenetic regulation on the effects of cancer cell migration, invasion and adhesion, provide experimental evidence for study on the health effects of human exposure to NPAHs.

英文关键词： N-PAHs;Lung caner metastasis;Hippo-YAP;Enhancer;Histone modification