高通量测序数据的深度解析表明腺苷至次黄苷碱基（A-to-I）RNA编辑是常见的遗传饰变，成为肿瘤研究的新热点。A-to-I编辑会引起lncRNA碱基序列改变，极可能影响其对靶基因的调控。课题组前期解析转录组数据揭示肺癌具有异常的编辑热点且存在过编辑现象；分析TCGA数据发现lncRNA SNHG3的A1746I和CEBPZ-AS的A1075/1126I高编辑与肺癌预后差有关。生物信息学预测上述三个位点可分别干扰其lncRNA结构稳定性或与RNA结合蛋白、微小RNA的结合，故推测上述A-to-I过编辑可影响lncRNA功能而促进肺癌的发生发展。本项目拟利用BASEscope技术检测临床样本上述3个A-to-I编辑的水平及其与肺癌发病和预后的关联；应用RNA编辑技术构建肺癌高编辑模式细胞系，通过系统的体内、体外研究，揭示A-to-I过编辑影响肺癌的生物学机制，为肺癌的分子靶向治疗提供科学依据。

Since the depth analysis of high-throughput sequencing data indicating that the adenosine to inosine (A-to-I) RNA editing is a common genetic modification, it has become a new hotspot in cancer research. The A-to-I editing can alter base sequence of host long non-coding RNA (lncRNA), which may influence the regulation of target coding genes. We have analyzed transcriptome data of lung cancer and found that lung cancer developed dysregulated editing hotspots and generally showed hyper-editing level. Based on the TCGA data, we further revealed three aberrant editing sites, A1746I and A1075/1126I that are respectively located in lncRNA SNHG3 and CEBPZ-AS to be significantly associated with poor lung cancer prognosis. Moreover, the bioinformatics analysis indicated that these A-to-I sites may alter structural stability of their host lncRNAs or the interaction between lncRNAs and RNA binding protein as well as microRNAs. Thus, we hypothesized that the high editing level of SNHG3 A1746I and CEBPZ-AS A1075/1126I can promote the development of lung cancer via interruption on function of their hosts. Here, this project intends to investigate the editing levels of above three A-to-I hotspots in clinical lung cancer samples and analysis their associations with the onset and prognosis of the disease using the BASEscope technology; To reveal the molecular mechanism underlying the biological effects of the A-to-I sites on lung cancer through a series of in vivo and in vitro experiments, which will be conducted on high editing pattern lung cancer cell lines that are constructed using the RNA editing for programmable A to I replacement system. The results from this project will provide effectively scientific evidences for molecular targeted therapy of lung cancer.