Gao Yifei, Yang Lei, Wang Ximo
Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Integrative Medicine for Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin Medical University Tianjin 300100, China.
Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Medical University Third Center Clinical College Tianjin 300170, China.
Am J Transl Res. 2025 May 15;17(5):3842-3861. doi: 10.62347/UNVS8140. eCollection 2025.
Cullin family genes play a critical role in ubiquitin-mediated protein degradation and have been implicated in various cancers. However, their expression patterns, prognostic significance, and functional roles in rectal adenocarcinoma (READ) remain unclear. This study aims to comprehensively analyze the expression, prognostic value, and potential biological functions of culllin genes in READ.
We analyzed the transcriptional expression of CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7, and CUL9 in READ using publicly available databases, including UALCAN and HOA. The prognostic significance of CUL genes was evaluated using Kaplan-Meier survival analysis. Functional enrichment analysis was performed to determine the biological pathways associated with cullin gene expression. Additionally, siRNA-mediated knockdown of CUL genes was done to assess the effect on cell proliferation, migration, and colony formation.
The analysis revealed significant overexpression of cullin genes in READ compared to normal tissues. Survival analysis indicated that higher expression of specific CUL2 and CUL7 genes correlated with poor prognosis in READ patients. Functional enrichment analysis demonstrated that cullin genes were associated with diverse enrichment terms. In vitro experiments showed that siRNA-mediated knockdown of CUL2 and CUL47 led to a significant reduction in cell proliferation, migration, and colony formation, highlighting their potential oncogenic role in READ.
This study provides novel insight into the role of cullin genes in READ, suggesting that CUL2 and CUL7 may be biomarkers and therapeutic targets. Further research is warranted to explore their underlying mechanisms and clinical applications in READ management.
Cullin家族基因在泛素介导的蛋白质降解中起关键作用，并与多种癌症有关。然而，它们在直肠腺癌（READ）中的表达模式、预后意义和功能作用仍不清楚。本研究旨在全面分析Cullin基因在READ中的表达、预后价值和潜在生物学功能。
我们使用公开可用的数据库，包括UALCAN和HOA，分析了READ中CUL1、CUL2、CUL3、CUL4A、CUL4B、CUL5、CUL7和CUL9的转录表达。使用Kaplan-Meier生存分析评估CUL基因的预后意义。进行功能富集分析以确定与Cullin基因表达相关的生物学途径。此外，进行了siRNA介导的CUL基因敲低，以评估对细胞增殖、迁移和集落形成的影响。
分析显示，与正常组织相比，READ中Cullin基因有显著过表达。生存分析表明，特定CUL2和CUL7基因的高表达与READ患者的不良预后相关。功能富集分析表明，Cullin基因与多种富集术语相关。体外实验表明，siRNA介导的CUL2和CUL47敲低导致细胞增殖、迁移和集落形成显著减少，突出了它们在READ中的潜在致癌作用。
本研究为Cullin基因在READ中的作用提供了新的见解，表明CUL2和CUL7可能是生物标志物和治疗靶点。有必要进一步研究以探索它们在READ管理中的潜在机制和临床应用。
