miRNAs可通过调节基因表达参与环境致癌物所致癌症的发生，但绝大多数miRNAs调控机制和生物功能尚不清楚。作为介导细胞外信号到细胞内反应的重要信号通路，MAPK过度激活与恶性肿瘤发生、发展、侵袭和转移密切相关。我们前期研究表明，B(a)P可引起特异性miRNAs表达改变，序列分析和初步实验表明miRNAs可能靶向MAPK通路中的关键基因对信号传导产生调节，影响肺癌发生发展，但作用机制有待阐明。针对筛选出的5个miRNAs，本研究应用细胞模型，构建目标miRNAs对MAPK信号通路的调控网络。进一步通过肺癌动物模型，初步阐明miRNAs调控MAPK通路在B(a)P诱导大鼠肺癌发生发展中的作用，并筛选可能的生物标志。最后通过病例-对照研究，验证目标miRNAs作为肺癌早期诊断、恶性评估和预后判断生物标志的可能。研究结果为进一步揭示环境致癌物引发肺癌发生的分子机制及肺癌防治提供依据。

miRNAs generally participate in cancer development induced by environmental carcinogen through gene expression regulationr, but the majority of regulatory mechanisms and biological functions of miRNAs is unclear. As an important signaling pathway mediated extracellular signal into intracellular reaction, over MAPK activation was closely related to tumorigenesis, development, invasion and metastasis of malignant tumors. Our previous studies showed that B (a) P can cause expression changes of specific miRNAs. Sequence analysis and preliminary experiments showed that miRNAs may regulate signal transduction and affect the development of lung cancer by targeting the key genes of MAPK pathway, but the action mechanism needs to be clarified. In this study, we selected five miRNAs and will build regulation network between target miRNAs and the MAPK signaling pathway by cell model study. Furthermore, we will preliminary clarify the role of miRNAs regulating MAPK pathway in the development of B(a)P-induced rat lung cancer by animal study, and screen potential biomarkers. Finally, we will verify the miRNAs biomarker for early diagnosis, malignant and prognostic evaluation of lung cancer by the case-control study. The results will supply the evidence for further revealing the molecular mechanisms triggered by environmental carcinogens and provide a basis for prevention and treatment of lung cancer.