结直肠癌（CRC）是一种侵袭性原发性肠道恶性肿瘤，在全球所有癌症类型中发病率排名第三，死亡率排名第二。转录因子 (TF) 能够识别基因上游的特定 DNA 序列，从而调节细胞发育和分化。大量研究表明 TF、肿瘤病因和治疗方法之间存在很强的相关性。在这里，我们的目的是探索与预后相关的转录因子并了解其致癌机制，从而为结直肠癌的诊断和治疗提供新的见解。利用癌症基因组图谱数据库、加权相关网络分析和技术，鉴定了结直肠癌和正常组织之间差异表达的转录因子。进行 Cox 回归分析以确定与预后相关的 TF。通过 5-乙炔基-2'-脱氧尿苷和 CRC 细胞中的细胞侵袭测定来确定中心 TF 锌指 E-box 结合同源框 1 (ZEB1) 的细胞功能。 RNA测序、京都基因和基因组百科全书富集以及基因集富集分析被用来鉴定ZEB1参与的细胞过程。通过免疫亲和纯化、银染质谱和染色质免疫沉淀分析来寻找可能与ZEB1及其共同调控的靶基因相互作用的蛋白。通过生物信息学分析技术鉴定出13个与预后相关的中心转录因子。通过结合调控网络图、生存曲线和表型分析确定，在这些 TF 中，ZEB1 是与 CRC 最密切相关的 TF。 ZEB1通过募集NuRD(MTA1)复合物促进CRC细胞生长，而ZEB1/NuRD(MTA1)复合物转录抑制糖酵解相关肿瘤抑制基因。我们的研究不仅鉴定了与CRC预后相关的中枢生物标志物，还揭示了特定分子ZEB1影响癌症进展的机制。这些见解为 CRC 的诊断和潜在的治疗机会提供了重要的证据。版权所有 © 2024 高、浩、张、霍、胡、马、于、滕、王、杨、黄和王。

Colorectal cancer (CRC) is an aggressive primary intestinal malignancy with the third-highest incidence and second-highest mortality among all cancer types worldwide. Transcription factors (TFs) regulate cell development and differentiation owing to their ability to recognize specific DNA sequences upstream of genes. Numerous studies have demonstrated a strong correlation between TFs, the etiology of tumors, and therapeutic approaches. Here, we aimed to explore prognosis-related TFs and comprehend their carcinogenic mechanisms, thereby offering novel insights into the diagnosis and management of CRC.Differentially expressed TFs between CRC and normal tissues were identified leveraging The Cancer Genome Atlas database, Weighted correlation network analysis and Cox regression analysis were performed to identify prognosis-related TFs. The cellular functions of hub TF zinc finger E-box binding homeobox 1 (ZEB1) were determined using by 5-ethynyl-2'-deoxyuridine and cell invasion assays in CRC cells. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes enrichment, and gene set enrichment analyses were used to identify the cellular processes in which ZEB1 participates. Immunoaffinity purification, silver staining mass spectrometry, and a chromatin immunoprecipitation assay were conducted to search for proteins that might interact with ZEB1 and the target genes they jointly regulate.Thirteen central TFs related to prognosis were identified through bioinformatics analysis techniques. Among these TFs, ZEB1 emerged as the TF most closely associated with CRC, as determined through a combination of regulatory network diagrams, survival curves, and phenotype analyses. ZEB1 promotes CRC cell growth by recruiting the NuRD(MTA1) complex, and the ZEB1/NuRD(MTA1) complex transcriptionally represses glycolysis-associated tumor suppressor genes.Our study not only identified a hub biomarker related to CRC prognosis but also revealed the specific molecular mechanisms through which ZEB1 affects cancer progression. These insights provide crucial evidence for the diagnosis of CRC and potential treatment opportunities.Copyright © 2024 Gao, Hao, Zhang, Huo, Hu, Ma, Yu, Teng, Wang, Yang, Huang and Wang.