结直肠癌（CRC）仍然是全球癌症相关死亡的第三大原因。在这里，我们的目的是揭示结直肠癌中转录因子第五尤文变异蛋白（FEV）的潜在机制。利用GSE143939、GSE142279、GSE196006和GSE200427数据集分析人结直肠癌及癌旁组织转录组差异表达，通过与Human TFBD数据库中的转录因子列表比较筛选交叉基因，然后进行KEGG富集分析。 CRC 中 FEV 表达显着降低，FEV 上调抑制 CRC 中细胞生长和肿瘤进展。 CRC中高表达的基因主要富集于Wnt信号通路，而WNT2是Wnt信号通路的核心启动子。 WNT2 启动子上有两个 FEV 结合位点。 WNT2促进CRC细胞的增殖、迁移和侵袭。 FEV 通过与 WNT2 启动子结合来抑制 WNT2 转录。总的来说，我们的数据表明，新的 FEV/WNT2 轴对于 CRC 进展至关重要。可以开发针对这一特定信号轴的策略来治疗 CRC 患者。在线版本包含可在 10.1007/s10616-024-00643-0 获取的补充材料。© 作者，获得 Springer Nature B.V. 2024 的独家许可。Springer Nature 或其许可方（例如协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议拥有本文的专有权；作者对本文已接受的手稿版本的自行存档仅受此类出版协议和适用法律的条款的约束。

Colorectal cancer (CRC) remains the third leading cause of cancer-related death worldwide. Here, we aimed to uncover the mechanism underlying the transcription factor fifth Ewing variant protein (FEV) in CRC. Transcriptome differential expression in human CRC and adjacent tissues was analyzed using GSE143939, GSE142279, GSE196006, and GSE200427 datasets, and the intersecting genes were screened by comparing them with the list of transcription factors in the Human TFBD database, followed by KEGG enrichment analysis. FEV expression was significantly reduced in CRC, and upregulation of FEV inhibited cell growth and tumor progression in CRC. The highly expressed genes in CRC were mainly enriched to the Wnt signaling pathway, and WNT2 is the core initiator of the Wnt signaling pathway. Two binding sites for FEV are present on the WNT2 promoter. WNT2 promoted the proliferation, migration, and invasion of CRC cells. FEV repressed WNT2 transcription by binding to the WNT2 promoter. Collectively, our data revealed that a novel FEV/WNT2 axis is critical for CRC progression. Strategies targeting this specific signaling axis might be developed to treat patients with CRC.The online version contains supplementary material available at 10.1007/s10616-024-00643-0.© The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.