EGR4 (Early Growth Response 4) is a member of the EGR family, involving in tumorigenesis. However, the function and action mechanism of EGR4 in the pathogenesis of colorectal cancer (CRC) remain unclear. To address this, we assessed the prognosis of CRC based on EGR4 using the Kaplan-Meier plotter tool and tissue microarray. The abundance of immunoinfiltration was evaluated through ssGSEA, TISIDB, and TIMER. In vitro experiments involving knockdown or overexpression of EGR4 were performed, and RNA-sequencing was conducted to explore potential mechanisms. Furthermore, we used oxaliplatin and 5-fluorouracil to validate the impact of EGR4 on chemo-resistance. Pan-cancer analysis and tissue microarray showed that EGR4 was highly expressed in CRC and significantly correlated with an unfavorable prognosis. Moreover, EGR4 expression was associated with immunoinfiltration and cancer-associated fibroblasts in the CRC microenvironment. Functional enrichment demonstrated that high-expressional EGR4 were involved in chromatin and nucleosome assembly. Additionally, EGR4 promoted the proliferation of CRC cells. Mechanistically, EGR4 upregulated TNFα to activate the NF-κB signaling pathway, and its knockdown reduced p65 nuclear translocation. Importantly, combining shEGR4 with oxaliplatin and 5-fluorouracil significantly inhibited CRC proliferation. Taken together, these findings provide new insights into the potential prognosis and therapeutic targets of EGR4 in CRC.

EGR4（早期生长反应4）是EGR家族的成员，参与肿瘤发生。然而，EGR4在结直肠癌（CRC）发病机制中的功能和作用机制仍不清楚。为了解决这个问题，我们使用 Kaplan-Meier 绘图仪工具和组织微阵列评估了基于 EGR4 的 CRC 预后。通过 ssGSEA、TISIDB 和 TIMER 评估免疫浸润的丰度。进行了涉及 EGR4 敲低或过度表达的体外实验，并进行了 RNA 测序以探索潜在的机制。此外，我们使用奥沙利铂和 5-氟尿嘧啶来验证 EGR4 对化疗耐药性的影响。泛癌分析和组织微阵列显示EGR4在结直肠癌中高表达，并与不良预后显着相关。此外，EGR4 表达与 CRC 微环境中的免疫浸润和癌症相关成纤维细胞相关。功能富集表明高表达的 EGR4 参与染色质和核小体组装。此外，EGR4促进CRC细胞的增殖。从机制上讲，EGR4 上调 TNFα 以激活​​ NF-κB 信号通路，其敲低可减少 p65 核转位。重要的是，shEGR4 与奥沙利铂和 5-氟尿嘧啶联合显着抑制 CRC 增殖。总而言之，这些发现为 EGR4 在 CRC 中的潜在预后和治疗靶点提供了新的见解。