长链非编码RNA在细颗粒物（PM2.5）诱导肺癌发生的作用与机制

项目名称： 长链非编码RNA在细颗粒物（PM2.5）诱导肺癌发生的作用与机制

项目编号： No.81473000

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 吴建军

作者单位： 广州医科大学

项目金额： 65万元

中文摘要： 我国各地雾霾天气不断增加，严重威胁着人民健康。环境细颗粒物（PM2.5）是雾霾形成的主要污染物，众多资料表明PM2.5长期暴露能显著增加肺癌等疾病的发生，但其致癌机制目前还不清楚。长链非编码RNA（lncRNA）广泛参与了环境化学物致癌过程。本项目拟以PM2.5为诱癌物，构建小鼠肺癌模型及细胞恶性转化模型，利用lncRNA芯片技术，分别检测两种模型中肺组织和转化细胞lncRNA差异表达谱，筛选出PM2.5诱导肺癌发生具有重要意义的lncRNA，然后建立gain-of-function和loss-of-function体系，采用荧光定量PCR、Northern Blot及CHIRP-Seq等研究手段探讨关键lncRNA在PM2.5诱导肺癌发生过程中的功能作用及分子机制。为研究lncRNA在PM2.5诱导肺肿瘤发生过程中的作用及机制提供重要的实验依据，也为PM2.5致癌机制研究开辟一种新思路。

中文关键词： 长链非编码RNA；细颗粒物；肺癌发生

英文摘要： Fog and haze weather is rising all over the country and seriously threat to people's health.Ambient fine particulate matter (PM2.5) are the main pollutants for haze formation.Many research data show that long-term exposure to PM2.5 can significantly increase the incidence of lung cancer and other diseases, but its carcinogenic mechanism is still unclear. Long non-coding RNA (lncRNA) extensively involved in the carcinogenesis induced by environmental chemicals.In present study. PM2.5 will be selected as carcinogens to induce lung carcinogenesis in mice and cell malignant transformation. Using lncRNA chip technology, the lncRNA differential expression profiles were detected in lung tissues of mice and transformed cells，respectively. We screened those key significant lncRNA invovling in PM2.5-induced lung carcinogenesis and established gain-of-function and loss-of-function system of lncRNA. Using fluorescence quantitative PCR, Northern Blot and CHIRP-Seq, we explored the fucnctions and mechanisms of key lncRNA during PM2.5-induced lung carcinogenesis. The present study will provide an important experimental basis for exploring the roles and mechanisms of lncRNA during PM2.5-induced lung tumorigenesis and create a new ideas for exploring the carcinogenic mechanism of PM2.5.

英文关键词： long non-coding RNA;PM2.5;lung carcinogenesis