结肠癌对人类健康构成重大威胁，给国民经济带来沉重负担。作为SOX转录因子家族的一员，SRY盒转录因子21（SOX21）与多种癌症相关，但其在结肠癌中的作用机制仍不清楚。本研究重点探讨转录因子SOX21在结肠癌细胞增殖和转移中的分子机制。我们通过生物信息学分析分析SOX21在结肠癌患者中的表达水平及其对生存的影响。我们使用公共数据库进行基因相关性、GSEA 富集分析。利用细胞功能实验（集落形成实验、伤口愈合实验、Transwell迁移和侵袭实验）来确定SOX21沉默和过表达对细胞增殖和转移的影响。荧光素酶报告基因检测，CUT

Colon cancer poses a major threat to human health and a heavy burden on the national economy. As a member of the SOX transcription factor family, SRY-box transcription factor 21 (SOX21) is associated with various cancers, but its mechanism of action in colon cancer remains unclear. This study focused on the molecular mechanisms of transcription factor SOX21 in proliferation and metastasis of colon cancer cells.We analyzed SOX21 expression level and its impact on survival in colon cancer patients by bioinformatics analysis. We used public databases for gene correlation, GSEA enrichment analysis. Cell function experiments (colony formation assay, wound healing assay, Transwell migration and invasion assay) were utilized to determine the impact of SOX21 silencing and over-expression on cell proliferation and metastasis. The luciferase reporter assay, CUT&RUN-qPCR assay and Methylation Specific PCR were used to explore SOX21-POU class 4 homeobox 2 (POU4F2) molecular interactions. The molecular mechanisms were verified by Quantitative real-time PCR and Western blot analysis.SOX21 is highly expressed and affects the overall survival of colon cancer patients. SOX21 can attenuates POU4F2 methylation state by binding with it. In addition, this interaction facilitate its transcriptional activation of Hedgehog pathway, mediates epithelial-mesenchymal transition (EMT), consequently promoting the proliferation and metastasis of colon cancer cells.Our study reveals that SOX21 is an oncogenic molecule and suggests its regulatory role in colon carcinogenesis and progression, providing new insights into the treatment of this disease.Copyright © 2024. Published by Elsevier Inc.