Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225001, P. R. China.
Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, P. R. China.
Int J Biol Sci. 2024 Sep 16;20(12):4978-4998. doi: 10.7150/ijbs.99590. eCollection 2024.
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 and . 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.
胃癌(GC)是全球第五大常见癌症和第四大癌症相关死亡原因。尽管在分子谱分析方面取得了进展,但驱动 GC 增殖和转移的机制仍不清楚。本研究确定早期 2 因子 4(E2F4)为关键转录因子,通过上调 DNA 复制和姐妹染色单体黏合蛋白 1(DSCC1)的表达促进 GC 细胞增殖、迁移和侵袭。生物信息学和转录因子分析显示 E2F4 是 DSCC1 的重要调节因子。功能分析证实了 E2F4 在增强 GC 细胞恶性表型中的作用。敲低和过表达实验表明 E2F4 可在转录水平上正向调控 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。这些发现强调了 E2F4-DSCC1 轴作为减轻 GC 进展的潜在治疗靶点的重要性。