Zhang Ruochen, Zhang Weijie, Zeng Yuanyuan, Li Yue, Zhou Jieqi, Zhang Yang, Wang Anqi, Lv Yantian, Zhu Jianjie, Liu Zeyi, Huang Jian-An
Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China.
Cell Death Discov. 2021 Nov 6;7(1):336. doi: 10.1038/s41420-021-00736-1.
Our previous studies revealed that oncogene CPNE1 is positively correlated with the occurrence, TNM stage, lymph node metastasis, and distant metastasis of non-small-cell lung cancer (NSCLC), and it could be regulated by micro RNAs. But no direct role of post-translational modification of CPNE1 in NSCLC has been reported. This study confirms that CPNE1 is degraded by two pathways: the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. CPNE1 binds with the ubiquitin molecule via its K157 residue. Moreover, we determined that the ubiquitin ligase NEDD4L can mediate the ubiquitination of CPNE1 and promote its degradation. In addition, we find that NEDD4L knockdown promotes the proliferation and metastasis of NSCLC cells by regulating CPNE1 in vitro and vivo. This study aims to further investigate the mechanism of CPNE1 ubiquitination in the occurrence and development of NSCLC and provide a new potential target for NSCLC treatment.
我们之前的研究表明，癌基因CPNE1与非小细胞肺癌（NSCLC）的发生、TNM分期、淋巴结转移及远处转移呈正相关，且其可受微小RNA调控。但尚未见关于CPNE1翻译后修饰在NSCLC中直接作用的报道。本研究证实CPNE1通过两条途径降解：泛素-蛋白酶体途径和自噬-溶酶体途径。CPNE1通过其K157残基与泛素分子结合。此外，我们确定泛素连接酶NEDD4L可介导CPNE1的泛素化并促进其降解。另外，我们发现敲低NEDD4L可在体外和体内通过调控CPNE1促进NSCLC细胞的增殖和转移。本研究旨在进一步探究CPNE1泛素化在NSCLC发生发展中的机制，并为NSCLC治疗提供一个新的潜在靶点。
