长链非编码RNAABHD11-AS1通过miR-182-5p/Tiam1-Rac1轴介导烟草致癌物NNK诱导肺癌发生的作用与机制

长链非编码RNA（lncRNA）在癌症发生过程中起着重要调控作用，在烟草致癌物NNK诱导的大鼠肺癌和恶性转化细胞模型基础上，我们发现lncRNA ABHD11-AS1影响细胞增殖和迁移介导NNK诱导肺癌发生，但其机制未明。生物信息学预测miR-182-5p与ABHD11-AS1存在特异性靶结合，并可靶作用于癌细胞迁移相关通路Tiam1-Rac1中的Tiam1。预实验显示， NNK转化的BEAS-2B细胞中，miR-182-5p表达下调且受ABHD11-AS1调控， Tiam1表达上调且Rac1信号通路被激活。我们推测：ABHD11-AS1可能通过miR-182-5p/Tiam1-Rac1轴介导NNK诱导肺癌发生。本项目拟从发展的观点，探讨NNK暴露过程中ABHD11-AS1介导肺癌发生发展的作用机制及时相性特征，为环境致癌物暴露的风险评估及寻找肺癌潜在分子标志、治疗新靶点提供科学依据。

Long non-coding RNA (lncRNA) plays an important regulatory role in the development of cancer. Based on the rat lung cancer and malignant transformed cell model induced by tobacco carcinogen NNK, we found that lncRNA ABHD11-AS1 mediates NNK-induced carcinogenesis by regulating cell proliferation and migration, but the mechanism is still not clear. Bioinformatics predict that miR-182-5p could specifically bind to ABHD11-AS1 and target at Tiam1 of Tiam1-Rac1 pathway, a cell migration-related pathway. The Results of our pre-experiments showed, the expression of miR-182-5p was down-regulated and regulated by ABHD11-AS1, and the expression of Tiam1 was up-regulated and Rac1 was activated in transformed BEAS-2B cell induced by NNK. We speculate that ABHD11-AS1 may mediate NNK-induced lung carcinogenesis through miR-182-5p/Tiam1-Rac1 axis. In this study, we will explore the role, mechanism and temporal characteristics of ABHD11-AS1 mediating lung carcinogenesis induced by NNK exposure from a developmental perspective, to provide scientific basis for the risk assessment of environmental carcinogens exposure and finding potential molecular markers and new therapeutic targets of lung cancer.