Zhao Zongquan, Feng Xinwei, Chen Bo, Wu Yihong, Wang Xiaohong, Tang Zhenyuan, Huang Min, Guo Xiaohua
Department of General Practice, Pingjiang New Town Community Health Service Center Sujin Street Gusu District, Suzho, 215000, Jiangsu, China.
Department of Digestive Internal Medicine, Shanghai Changzheng Hospital, Shanghai, 200003, China.
Hereditas. 2025 Feb 10;162(1):19. doi: 10.1186/s41065-025-00368-w.
The study investigates the role of Cell Division Cycle Associated (CDCA) genes in colorectal cancer (COAD) by analyzing their differential expression, epigenetic alterations, prognostic significance, and functional associations.
This study employed a detailed in silico and in vitro experiments-based methodology.
RT-qPCR assays reveal significantly elevated mRNA levels of CDCA2, CDCA3, CDCA4, CDCA5, CDCA7, and CDCA8 genes in COAD cell lines compared to controls. Bisulfite sequencing indicates reduced promoter methylation of CDCA gene promoters in COAD cell lines, suggesting an epigenetic regulatory mechanism. Analysis of large TCGA datasets confirms increased CDCA gene expression in COAD tissues. Survival analysis using cSurvival database demonstrates negative correlations between CDCA gene expression and patient overall survival. Additionally, Lasso regression-based models of CDCA genes predict survival outcomes in COAD patients. Investigating immune modulation, CDCA gene expression inversely correlates with immune cell infiltration and immune modulators. miRNA-mRNA network analysis identifies regulatory miRNAs targeting CDCA genes, validated by RT-qPCR showing up-regulation of has-mir-10a-5p and has-mir-20a-5p in COAD cell lines and tissues. Drug sensitivity analysis suggests resistance to specific drugs in COAD patients with elevated CDCA gene expression. Furthermore, CDCA gene expression correlates with crucial functional states in COAD, including "angiogenesis, apoptosis, differentiation, hypoxia, inflammation, and metastasis." Additional in vitro experiments revealed that CDCA2 and CDCA3 knockdown in SW480 and SW629 cells significantly reduced cell proliferation and colony formation while enhancing cell migration.
Overall, the study elucidates the multifaceted role of CDCA genes in COAD progression, providing insights into potential diagnostic, prognostic, and therapeutic implications.
本研究通过分析细胞分裂周期相关（CDCA）基因的差异表达、表观遗传改变、预后意义和功能关联，探讨其在结直肠癌（COAD）中的作用。
本研究采用了基于计算机模拟和体外实验的详细方法。
RT-qPCR分析显示，与对照组相比，COAD细胞系中CDCA2、CDCA3、CDCA4、CDCA5、CDCA7和CDCA8基因的mRNA水平显著升高。亚硫酸氢盐测序表明，COAD细胞系中CDCA基因启动子的甲基化减少，提示存在表观遗传调控机制。对大型TCGA数据集的分析证实，COAD组织中CDCA基因表达增加。使用cSurvival数据库进行的生存分析表明，CDCA基因表达与患者总生存期呈负相关。此外，基于套索回归的CDCA基因模型可预测COAD患者的生存结果。在免疫调节方面，CDCA基因表达与免疫细胞浸润和免疫调节因子呈负相关。miRNA-mRNA网络分析确定了靶向CDCA基因的调控miRNA，RT-qPCR验证显示，COAD细胞系和组织中has-mir-10a-5p和has-mir-20a-5p上调。药物敏感性分析表明，CDCA基因表达升高的COAD患者对特定药物耐药。此外，CDCA基因表达与COAD中的关键功能状态相关，包括“血管生成、细胞凋亡、分化、缺氧、炎症和转移”。额外的体外实验表明，在SW480和SW629细胞中敲低CDCA2和CDCA3可显著降低细胞增殖和集落形成，同时增强细胞迁移。
总体而言，本研究阐明了CDCA基因在COAD进展中的多方面作用，为潜在的诊断、预后和治疗意义提供了见解。
