胃癌（GC）是全球第五大常见癌症，也是全球癌症相关死亡的第四大原因。尽管分子谱分析取得了进展，但驱动GC增殖和转移的机制仍不清楚。本研究将早期 2 因子 4 (E2F4) 确定为关键转录因子，通过上调 DNA 复制和姐妹染色单体凝聚 1 (DSCC1) 表达来促进 GC 细胞增殖、迁移和侵袭。生物信息学和转录因子分析表明 E2F4 是 DSCC1 的重要调节因子。功能测定证实了 E2F4 在体内外增强 GC 细胞恶性程度的作用。敲低和过表达实验表明，E2F4 在转录水平上正向调节 DSCC1，ChIP-qPCR 和双荧光素酶报告基因检测验证了 DSCC1 启动子上的结合位点。这些发现强调 E2F4-DSCC1 轴是减缓 GC 进展的潜在治疗靶点。© 作者。

Gastric cancer (GC) ranks as the fifth most common cancer and the fourth leading cause of cancer-related deaths globally. Despite advancements in molecular profiling, the mechanisms driving GC proliferation and metastasis remain unclear. This study identifies Early 2 Factor 4 (E2F4) as a key transcription factor that promotes GC cell proliferation, migration, and invasion by upregulating DNA Replication and Sister Chromatid Cohesion 1 (DSCC1) expression. Bioinformatics and transcription factor analyses revealed E2F4 as a significant regulator of DSCC1. Functional assays confirmed E2F4's role in enhancing GC cell malignancy in vitro and in vivo. Knockdown and overexpression experiments demonstrated that E2F4 positively regulates DSCC1 at the transcriptional level, with ChIP-qPCR and dual luciferase reporter assays validating the binding sites on the DSCC1 promoter. These findings highlight the E2F4-DSCC1 axis as a potential therapeutic target to mitigate GC progression.© The author(s).