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转录因子 E2F4 通过转录激活 DSCC1 促进胃癌细胞的增殖、迁移和侵袭。

Transcription Factor E2F4 Promote Proliferation, Migration, and Invasion of Gastric Cancer Cells by transcriptionally activating DSCC1.

机构信息

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.

出版信息

Int J Biol Sci. 2024 Sep 16;20(12):4978-4998. doi: 10.7150/ijbs.99590. eCollection 2024.

DOI:10.7150/ijbs.99590
PMID:39309429
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11414385/
Abstract

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.

摘要

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。

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