tRNA作为蛋白质合成基础元件过量地存于细胞内（冗余性）。新近研究显示，改变某一种tRNA或tRNA修饰酶水平，可影响肿瘤发生、转移，提示tRNA在肿瘤发生、恶性进展过程中有一定的调控作用。申请人前期参与了tRNA羧甲基修饰酶Elongator与乳腺癌转移相关性的研究。本项目申请旨在进一步揭示Elongator参与的肿瘤生物学作用与机制，探索其靶标意义。前期功能相关密码子使用分析与实验筛查结果表明，Elongator参与调控细胞周期进行、有丝分裂蛋白表达，TCGA数据分析显示受Elongator调控的有丝分裂蛋白高表达于肺腺癌，与患者预后呈显著负相关。进而，本研究拟在细胞、转基因小鼠和临床标本水平系统阐明Elongator对肺腺癌有丝分裂的调控作用与分子机制，确立本课题相关分子的肿瘤标志物意义，揭示Elongator酶促tRNA修饰参与的肺腺癌有丝分裂调控机制，为肺腺癌治疗提供新潜在靶标。

tRNA is overexpressed in cells with redundancy, and constitutes the basic module for protein translation. However, it has been recently discovered that the overexpression of some specific tRNA can drive cancer progression, meanwhile the less-expression of tRNA-modification enzyme can regulate tumorigenicity, or make tumor less metastatic. The applicant has joined one project related to the role of carboxymethyl introducing tRNA-modification enzyme Elongator in breast cancer metastasis. In this project, those codon whose decode highly depends upon Elongator, was first analyzed. The bioinformatics analysis and preliminary results indicate that Elongator can regulate cell cycle progression, and mitotic genes’ expression. Those mitotic genes regulated by Elongator, are overexpressed in lung adenocarcinoma, and those genes’ overexpression shows remarkable negative correlation with the survival of lung adenocarcinoma patients. Accordingly, this project is planned to use lung adenocarcinoma cell line, transgenic mouse model, and clinical samples, to do in-depth research upon the role of Elongator in mitosis, its molecular mechanism involved, and its translational meaning. All the work will help to understand how Elongator catalyzed tRNA modification regulates lung adenocarcinoma at mitotic level, and will also give rise to new potential targets for cancer target therapy.