转录因子 E2F4 通过转录激活 DSCC1 促进胃癌细胞增殖、迁移和侵袭

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Shantanu Baral, Yantao Yu, Qiannan Sun, Mingrui Jiang, Ruiqi Li, Yifan Cheng, Arawker Mubeen Hussein, Youquan Shi, Yongjun Jiang, Dong Tang, Sen Wang, Daorong Wang
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引用次数: 0

摘要

胃癌(GC)是全球第五大常见癌症,也是导致癌症相关死亡的第四大原因。尽管分子图谱分析取得了进展,但胃癌增殖和转移的驱动机制仍不清楚。本研究发现,早期2因子4(E2F4)是一种关键的转录因子,它通过上调DNA复制和姐妹染色单体内聚1(DSCC1)的表达,促进GC细胞的增殖、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。功能测试证实了 E2F4 在体外和体内增强 GC 细胞恶性程度的作用。基因敲除和过表达实验表明,E2F4 在转录水平上对 DSCC1 起着积极的调控作用,ChIP-qPCR 和双荧光素酶报告实验验证了 DSCC1 启动子上的结合位点。这些发现凸显了 E2F4-DSCC1 轴是缓解 GC 进展的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transcription Factor E2F4 Promote Proliferation, Migration, and Invasion of Gastric Cancer Cells by transcriptionally activating DSCC1
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.
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来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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