Yang Zhen, Huang Rongkun, Yang Yun, Cong Jing, Yang Xia, Zhou Quan, Guo Ruoyu, Ma Ying, Gong Xiangqian, Jiao Fei, Li Youjie, Zhu Shugang, Kong Lijun, Hu Jinxia
Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, China.
Institute of Healthcare and Industry, Sichuan Tourism College, Chengdu, Sichuan 610000, China.
J Cancer. 2024 Aug 13;15(16):5149-5164. doi: 10.7150/jca.98238. eCollection 2024.
To explore the roles of Neural precursor cell expressed developmentally down-regulated 1(NEDD1) in lung cancer tumorigenesis and the relationship between NEDD1 expression and clinicopathology of patients with lung adenocarcinoma (LUAD). : Expression of NEDD1 or other proteins in tissues and cell lines were determined with immunohistochemistry or western blot, the data of patients with LUAD in The Cancer Genome Atlas (TCGA) datasets and LUAD tissue array were collected and analyzed, the effects of NEDD1 on proliferation, migration, cell cycle progression and apoptosis of cancer cells were detected with colony formation assay, transwell assay and Flow cytometry (FCM) analysis respectively. the impact of NEDD1 knockdown on DNA damage was analyzed using Immunofluorescence staining of H2AX and comet assay. Furthermore, the effect of NEDD1 on cancer cell proliferation was investigated in nude mice. NEDD1 was upregulated in lung tissues and the NEDD1 immune score was an independent prognostic factor. Overexpression of NEDD1 promoted epithelial-mesenchymal transition, accelerated cell cycle progression, and enhanced the proliferation and migration of A549 and H1299 cells, while knockdown of NEDD1 resulted in the opposite phenotype and leaded to DNA damage. In addition, NEDD1 improved cell tumorigenicity . These findings suggest that NEDD1 plays important roles in lung cancer development and may therefore be a potential prognostic marker and promising therapeutic target for lung cancer therapy.
探讨神经前体细胞表达发育下调蛋白1（NEDD1）在肺癌发生中的作用以及NEDD1表达与肺腺癌（LUAD）患者临床病理特征之间的关系。：采用免疫组织化学或蛋白质印迹法检测组织和细胞系中NEDD1或其他蛋白的表达，收集并分析癌症基因组图谱（TCGA）数据集和LUAD组织芯片中LUAD患者的数据，分别采用集落形成试验、Transwell试验和流式细胞术（FCM）分析检测NEDD1对癌细胞增殖、迁移、细胞周期进程和凋亡的影响。采用H2AX免疫荧光染色和彗星试验分析NEDD1敲低对DNA损伤的影响。此外，在裸鼠中研究了NEDD1对癌细胞增殖的影响。NEDD1在肺组织中上调，且NEDD1免疫评分是一个独立的预后因素。NEDD1的过表达促进上皮-间质转化，加速细胞周期进程，并增强A549和H1299细胞的增殖和迁移，而敲低NEDD1则导致相反的表型并导致DNA损伤。此外，NEDD1提高了细胞的致瘤性。这些发现表明，NEDD1在肺癌发展中起重要作用，因此可能是一种潜在的预后标志物和有前景的肺癌治疗靶点。
