Forkhead Box M1（FOXM1）是转录因子Forkhead Box家族中的重要成员，有助于介导肿瘤形成。然而，对于FOXM1基因调控的机制性认识仍有限。DEAD-box RNA解旋酶家族的典型成员DDX5（p68）通过调节RNA代谢和转录共激活转录因子，在癌症进程中表现出多方面的作用。在这里，我们报道了DDX5（p68）和Wnt/β-catenin途径在调控FOXM1基因表达和促进结肠癌形成方面联盟的新机制。初步的生物信息学分析显示结直肠癌数据集中FOXM1和DDX5（p68）的表达水平升高。免疫组织化学分析证实FOXM1在正常和结肠癌患者样本中与DDX5（p68）和β-catenin呈正相关。DDX5（p68）和β-catenin的过表达增加了FOXM1蛋白和mRNA表达水平，而下调时相反。在机制上，DDX5（p68）和β-catenin的过表达和沉默升高和降低了FOXM1的启动子活性。此外，染色质免疫共沉淀实验证明DDX5（p68）和β-catenin在FOXM1启动子的TCF4/LEF结合位点（TBE）处有占位。Thiostrepton描绘了FOXM1抑制对细胞增殖和迁移的影响。集落形成实验、迁移实验和细胞周期数据揭示了DDX5（p68）/β-catenin/FOXM1轴在肿瘤形成中的重要性。总之，我们的研究在机械上突出了DDX5（p68）和β-catenin在结直肠癌中调节FOXM1基因表达的作用。© 2023 Elsevier B.V. 发布。

Forkhead box M1 (FOXM1), a vital member of the Forkhead box family of transcription factors, helps in mediating oncogenesis. However, limited knowledge exists regarding the mechanistic insights into the FOXM1 gene regulation. DDX5 (p68), an archetypal member of the DEAD-box family of RNA helicases, shows multifaceted action in cancer progression by arbitrating RNA metabolism and transcriptionally coactivating transcription factors. Here, we report a novel mechanism of alliance between DDX5 (p68) and the Wnt/β-catenin pathway in regulating FOXM1 gene expression and driving colon carcinogenesis. Initial bioinformatic analyses highlighted elevated expression levels of FOXM1 and DDX5 (p68) in colorectal cancer datasets. Immunohistochemical assays confirmed that FOXM1 showed a positive correlation with DDX5 (p68) and β-catenin in both normal and colon carcinoma patient samples. Overexpression of DDX5 (p68) and β-catenin increased the protein and mRNA expression profiles of FOXM1, and the converse correlation occurred during downregulation. Mechanistically, overexpression and knockdown of DDX5 (p68) and β-catenin elevated and diminished FOXM1 promoter activity respectively. Additionally, Chromatin immunoprecipitation assay demonstrated the occupancy of DDX5 (p68) and β-catenin at the TCF4/LEF binding element (TBE) sites on the FOXM1 promoter. Thiostrepton delineated the effect of FOXM1 inhibition on cell proliferation and migration. Colony formation assay, migration assay, and cell cycle data reveal the importance of the DDX5 (p68)/β-catenin/FOXM1 axis in oncogenesis. Collectively, our study mechanistically highlights the regulation of FOXM1 gene expression by DDX5 (p68) and β-catenin in colorectal cancer.Copyright © 2023. Published by Elsevier B.V.