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第三高,死亡率第二高。转录因子(TF)由于其识别基因上游的特定DNA序列的能力而调节细胞发育和分化。大量研究表明,TFs之间存在很强的相关性,肿瘤的病因,和治疗方法。这里,我们旨在探索与预后相关的TFs并理解其致癌机制,从而为CRC的诊断和管理提供了新的见解。
■利用癌症基因组图谱数据库鉴定CRC和正常组织之间差异表达的TFs,进行加权相关网络分析和Cox回归分析以鉴定与预后相关的TFs。使用5-乙炔基-2'-脱氧尿苷和CRC细胞中的细胞侵袭测定法确定了hubTF锌指E盒结合同源盒1(ZEB1)的细胞功能。RNA测序,京都基因和基因组富集百科全书,和基因集富集分析用于鉴定ZEB1参与的细胞过程。免疫亲和纯化,银染质谱,并进行染色质免疫沉淀测定以搜索可能与ZEB1和它们共同调节的靶基因相互作用的蛋白质。
■通过生物信息学分析技术鉴定了13种与预后相关的中心TFs。在这些TFs中,ZEB1成为与CRC最密切相关的TF,通过监管网络图的组合确定,存活曲线,和表型分析。ZEB1通过招募NuRD(MTA1)复合物促进CRC细胞生长,和ZEB1/NuRD(MTA1)复合物转录抑制糖酵解相关的肿瘤抑制基因。
■我们的研究不仅确定了与CRC预后相关的中心生物标志物,而且揭示了ZEB1影响癌症进展的特定分子机制。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。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.