miRNAs通过转录后调控靶基因广泛参与肿瘤发生发展的各个阶段。Ago2蛋白是miRNAs通路的核心效应分子，对维持整个miRNAs网络的稳定性至关重要，也是肺癌患者不良预后的潜在高风险因素。在前期工作中，我们鉴定了TBK1介导的Ago2蛋白S417位点磷酸化修饰；功能学实验证明：S417磷酸化能够显著增强肺癌细胞的生长增殖能力；临床数据分析发现：肺癌患者中存在S417磷酸化增强的Ago2临床位点突变；分子机制初步探究表明：S417磷酸化能够促进miRNAs loading过程，特异性增强部分miRNAs功能。在前期工作基础上，本项目将深入研究Ago2蛋白S417磷酸化修饰在非小细胞肺癌发生发展中的生物学功能，重点阐明其对特异性miRNAs群体的选择性调控机制，通过特异性p-S417磷酸化抗体进行大样本检测和突变率筛查，系统性评估其潜在临床应用价值，旨为开发新治疗靶点和新标志物奠定基础。

miRNAs are widely involved in all stages of tumorigenesis through post-transcriptional regulation of target genes. Ago2 is not only the core effector of miRNAs pathway, and is essential for maintaining the stability of the miRNAs network, but also a potential high risk factor of poor prognosis of lung cancer patients. In the previous work, we identified the TBK1-mediated phosphorylation of Ago2 at S417 site. Functional experiments showed that S417 phosphorylation can significantly enhance the capability of cell proliferation. Clinical datas analysis revealled that natives mutation of Ago2 with high S417 phosphorylation capacity present in clinical lung cancer patients. Molecular mechanisms studies indicated that S417 phosphorylation can promote the miRNAs loading process and enhance the function of specific miRNAs groups. Based on the previous work, the project will further expore the biological function of S417 phosphorylation in the progression of non-small cell lung cancer, elucidate the selective regulation mechanism for specific miRNAs groups. Systematically evaluate the potential clinical application value of S417 phosphorylation through screening in large number of clinical samples by specific p-S417 antibody and mutation screening. The aim of this study is to expore new therapeutic targets and new markers.