Ma Jinyang, Lang Bojuan, Wang Lei, Zhou Youdong, Fu Changtao, Tian Chunlei, Xue Lixin
Department of Neurology, The First College of Clinical Medical Sciences, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, Hubei, People's Republic of China.
Department of Pathology, The First College of Clinical Medical Sciences, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, Hubei, People's Republic of China.
Mol Biotechnol. 2025 Jun;67(6):2286-2304. doi: 10.1007/s12033-024-01197-4. Epub 2024 Jun 5.
Cell cycle exit and neuronal differentiation 1 (CEND1), highly expressed in the brain, is a specific transmembrane protein which plays a tumor suppressor role. This study is performed to investigate the role of CEND1 in various cancers through pan-cancer analysis, and further investigate its functions in gliomas by cell experiments. The expression and subcellular localization of CEND1 in different cancer types were analyzed utilizing the data from the GEPIA, UCSC, UALCAN and HPA databases. Relationships of CEND1 expression with prognosis, immunomodulation-related genes, immune checkpoint genes, microsatellite instability (MSI), tumor mutation burden (TMB) and RNA modifications were analyzed based on the TCGA database. The ESTIMATE algorithm was utilized to evaluate tumors' StromalScore, Immune Score, and ESTIMATES Score. The cBioPortal database was employed to analyze the categories and frequencies of CEND1 gene alterations. Biological functions and co-expression patterns of CEND1 in gliomas were explored using the LinkedOmics database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. The interactions between CEND1 and drugs were explored employing the Comparative Toxicogenomics Database and molecular docking technology. Cell experiments were conducted to analyze triptonide's effects on glioma cells through CCK-8, flow cytometry and qRT-PCR. CEND1 was lowly expressed in gliomas, and high CEND1 expression was correlated to better overall survival of glioma patients (HR = 0.65, P = 0.02). Deep deletion was the main type of hereditary change of CEND1 mutation. CEND1 expression was markedly associated with immune infiltration, TMB, MSI, and RNA modification in various tumors (r > 0.3, P < 0.05). CEND1 co-expressed genes in gliomas were markedly correlated with immune responses and cell cycle (FDR < 0.05). Triptonide could bind well to CEND1 (-5.0 kcal/mol), and triptonide could facilitate CEND1 expression in glioma cells and cell apoptosis, and block the cell cycle progression (P < 0.05). CEND1 serves as a potential biomarker for pan-cancer. Particularly in gliomas, CEND1 is a key regulator of cell apoptosis and cell cycle, and a potential target for glioma treatment.
细胞周期退出与神经元分化蛋白1（CEND1）在大脑中高度表达，是一种具有肿瘤抑制作用的特异性跨膜蛋白。本研究旨在通过泛癌分析探讨CEND1在各种癌症中的作用，并通过细胞实验进一步研究其在胶质瘤中的功能。利用GEPIA、UCSC、UALCAN和HPA数据库的数据，分析了CEND1在不同癌症类型中的表达和亚细胞定位。基于TCGA数据库，分析了CEND1表达与预后、免疫调节相关基因、免疫检查点基因、微卫星不稳定性（MSI）、肿瘤突变负荷（TMB）和RNA修饰之间的关系。采用ESTIMATE算法评估肿瘤的基质评分、免疫评分和ESTIMATES评分。利用cBioPortal数据库分析CEND1基因改变的类别和频率。使用LinkedOmics数据库探索CEND1在胶质瘤中的生物学功能和共表达模式，并进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。利用比较毒理基因组学数据库和分子对接技术探索CEND1与药物之间的相互作用。通过CCK-8、流式细胞术和qRT-PCR进行细胞实验，分析雷公藤内酯醇对胶质瘤细胞的影响。CEND1在胶质瘤中低表达，CEND1高表达与胶质瘤患者更好的总生存期相关（HR = 0.65，P = 0.02）。深度缺失是CEND1突变的主要遗传改变类型。CEND1表达与各种肿瘤中的免疫浸润、TMB、MSI和RNA修饰显著相关（r > 0.3，P < 0.05）。CEND1在胶质瘤中的共表达基因与免疫反应和细胞周期显著相关（FDR < 0.05）。雷公藤内酯醇能与CEND1良好结合（-5.0 kcal/mol），雷公藤内酯醇能促进胶质瘤细胞中CEND1的表达和细胞凋亡，并阻断细胞周期进程（P < 0.05）。CEND1作为一种潜在的泛癌生物标志物。特别是在胶质瘤中，CEND1是细胞凋亡和细胞周期的关键调节因子，也是胶质瘤治疗的潜在靶点。
