端粒酶是一种主要由蛋白亚基hTERT和RNA亚基hTER组成的逆转录酶，超过85%的肿瘤中端粒酶都高表达。存在于hTERT启动子上的两个突变热点在一系列肿瘤发生中起重要作用，而在肺癌中，此种突变率非常低，具体的激活端粒酶的机制还不清楚。通过酵母三杂交的方法，筛选到了与两种与hTERT5’UTR相互作用的蛋白CMSS1和RBM34；进一步研究发现，两者可以通过与DDX5等蛋白形成复合体一起调控端粒酶的活性。并且我们发现CMSS1与肺癌的发生有着密切的关系：CMSS1、RBM34和hTERT在肺癌组织中高表达，并且高表达CMSS1或RBM34的肺癌病人生存率低。基于此，我们提出，CMSS1通过与RBM34、DDX5等蛋白形成复合体来激活端粒酶并参与到非小细胞肺癌的发生发展的过程中。本课题拟通过一系列体内体外的实验系统研究这种作用机制，并结合肺癌临床标本进行验证，明确其临床意义。

Telomere elongation by telomerase plays an essential role in human cancer and aging. In humans, the core telomerase complex contains the catalytic protein subunit (hTERT) and the RNA subunit (hTER). Telomerase up-regulation is observed in more than 85% of human cancers. Two somatic mutations in the TERT promoter (C228T; C250T) have been identified which activation of telomerase in multiple cancers. However, TERT promoter mutations are infrequent in patients with lung cancer (<5%) and the mechanism of telomerase activation in lung cancer is still unknown. In this study, CMSS1 and RBM34 interacting with hTERT 5'UTR were screened by yeast three-hybrid and CMSS1 regulate telomerase by forming a complex with RBM34 and DDX5. CMSS1, RBM34, and hTERT are highly expressed in lung cancer tissues compared with normal tissues, and lung cancer patients with higher expression of CMSS1 and RBM34 have a worse prognosis. Based on these data, we propose that CMSS1/RBM34/DDX5 complex activates telomerase and involves in the development of non-small cell lung cancer. This study aims to study the new mechanism of telomerase regulation by CMSS1/RBM34/DDX5 complex and its role in the development of non-small cell lung cancer and uncover the clinical significance of CMSS1 in non-small cell lung cancer.