hTERT高表达是肿瘤发生发展的风向指标，深入研究hTERT调控机制非常必要。预实验中我们采用新的启动子结合蛋白垂钓鉴定系统，成功垂钓出hTERT调控因子RFPL3；并发现肺癌细胞中RFPL3特异性地结合hTERT启动子，激活其转录活性，影响细胞生长和凋亡。但RFPL3在调控hTERT及肺癌发生发展中具体的作用和机制及临床意义，尚不清楚。为此，本项目拟过表达或敲低RFPL3基因，在细胞及动物模型中，进一步研究RFPL3对hTERT表达、端粒酶活性、端粒长度，细胞生长和凋亡、肿瘤形成、以及相关信号通路的影响，进而明确RFPL3的生物学功能和分子机制。另外，采用组织芯片等技术，分析RFPL3和hTERT在肺癌组织中的表达，并结合临床资料评估其与肺癌分期、生存、转移、复发等的相关性，确定其临床意义。本项目将为揭示肺癌发生发展机制提供新认识，也为确立RFPL3作为肿瘤治疗新靶点提供理论和实验依据。

hTERT is the hallmarker of tumorigenesis.It is necessary to discover and identify novel regulatory mechanisms of hTERT.In the earlier studies, we used a novel system to pull down and identify promoter-binding proteins and found that in lung cancer cells RFPL3 tumor-specifically binds to hTERT promoter, activates its transcriptional activity, and affects tumor cell growth and apoptosis. However, the action mechanisms by which RFPL3 regulates hTERT　and lung cancer growth and development as well as its clinical implications remain unclear. In this study, we will overexpress and knockdown RFPL3 gene to further study the effects of RFPL3 on hTERT expression,telomerase activity, telomere length,cell growth and apoptosis, tumor formation, and the signaling pathway involving in tumor development and progression in cell and animal models, thereby identifying the biological functions and molecular mechanisms of RFPL3. Moreover, we will also analyze RFPL3 and hTERT expression in tumor tissues by tissue array and evaluate correlation of RFPL3 with lung cancer stage, survival,metastasis, recurrence by combining the clinical data, thereby identifying the clinical implications of RFPL3.This program will provide new understanding for identification of the mechanisms of lung cancer development and progression, and provide theoretical and experimental basis for the development of RFPL3 as a new therepeutic target for cancers.