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

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.

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。

环境细颗粒物（PM2.5）污染问题日益引起广大民众重视，PM2.5污染增加了人群肺癌等呼吸系统疾病发病率，但其作用与机制还不清楚。长链非编码RNA（lncRNA）近年来被认为在疾病发生发展过程中发挥着重要作用。本项目以PM2.5样本急性和慢性处理人支气管上皮细胞16HBE，分别构建PM2.5急性处理16HBE细胞模型和PM2.5诱导的16HBE恶性转化细胞模型，进行lncRNA和mRNA基因表达谱分析，发现PM2.5急慢性暴露均可以导致lncRNA和mRNA表达谱发生改变。PM2.5急性暴露16HBE细胞可抑制细胞增殖能力并导致G2/M期阻滞，同时我们发现lncRNA LINC00341异常高表达，通过荧光定量PCR、siRNA及Western Blot一系列实验验证，揭示了LINC00341可能通过调节p21蛋白介导PM2.5诱导的细胞增殖抑制和周期阻滞。在低剂量PM2.5诱导恶性细胞转化模型中，我们发现，低剂量细颗粒物的长期暴露，可以促进人支气管上皮细胞增殖，同时伴有细胞周期阻滞及炎症反应。同时诱导lncRNA表达谱改变，我们的结果揭示了，在PM2.5诱导支气管上皮细胞转化过程中，lncRNA LINC01433可能通过调控细胞周期改变，从而诱导细胞增殖，促使细胞发生恶性转化的作用机制。