KLF4通过激活STAT3促进EMT诱发结直肠癌

IF 2.5 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY
Digestive Diseases and Sciences Pub Date : 2024-08-01 Epub Date: 2024-05-30 DOI:10.1007/s10620-024-08473-y
Lebin Yuan, Yanqiu Meng, Jiajia Xiang
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引用次数: 0

摘要

目的:Krüppel样因子4(KLF4)已被证实在实体组织中具有促癌作用。目的:研究 KLF4 是否参与了 CRC 的增殖和侵袭:方法:使用免疫组织化学和免疫印迹法研究 KLF4 的表达。方法:采用免疫组织化学和免疫印迹法研究 KLF4 的表达,评估 KLF4 的临床意义。此外,还研究了抑制或过表达 KLF4 对肿瘤的影响。免疫印迹和 qPCR 被用来检测上皮-间质转化相关蛋白的水平。此外,还通过JASPAR、GSEA分析和体外实验确定了KLF4与STAT3信号通路相关的分子功能:结果:KLF4在CRC中表现出下调表达,是血管侵袭、TNM分期和预后恶化的一部分。体外研究表明,KLF4 可促进细胞增殖和侵袭以及 EMT 过程。异种移植肿瘤模型证实了 KLF4 在裸鼠中的致癌作用。此外,GSEA 和 JASPAR 数据库分析表明,KLF4 与信号转导子和转录激活子 3(STAT3)启动子位点结合可诱导 p-STAT3 信号的激活。随后的STAT3靶向研究证实了其在介导KLF4致癌效应中的关键作用:该研究表明,KLF4 可激活 STAT3 信号,诱导上皮-间质转化,从而促进 CRC 的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

KLF4 Induces Colorectal Cancer by Promoting EMT via STAT3 Activation.

KLF4 Induces Colorectal Cancer by Promoting EMT via STAT3 Activation.

Objective: Krüppel-like factor 4 (KLF4) has been demonstrated to exert a pro-carcinogenic effect in solid tissues. However, the precise biological function and underlying mechanisms in colorectal cancer (CRC) remains elucidated.

Aims: To investigate whether KLF4 participates in the proliferation and invasion of CRC.

Methods: The expression of KLF4 was investigated using immunohistochemistry and immunoblotting. The clinical significance of KLF4 was evaluated. Furthermore, the effect of inhibiting or overexpressing KLF4 on tumor was examined. Immunoblotting and qPCR were used to detect Epithelial-mesenchymal transition-related proteins levels. Additionally, the molecular function of KLF4 is related to the STAT3 signaling pathway and was determined through JASPAR, GSEA analysis, and in vitro experiments.

Results: KLF4 exhibits down-regulated expression in CRC and is part of the vessel invasion, TNM stage, and worse prognosis. In vitro studies have shown that KLF4 promotes cellular proliferation and invasion, as well as EMT processes. Xenograft tumor models confirmed the oncogenic role of KLF4 in nude mice. Furthermore, GSEA and JASPAR databases analysis reveal that the binding of KLF4 to the signal transducer and activator of transcription 3 (STAT3) promoter site induces activation of p-STAT3 signaling. Subsequent targeting of STAT3 confirmed its pivotal role in mediating the oncogenic effects exerted by KLF4.

Conclusion: The study suggests that KLF4 activates STAT3 signaling, inducing epithelial-mesenchymal transition, thereby promoting CRC progression.

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来源期刊
Digestive Diseases and Sciences
Digestive Diseases and Sciences 医学-胃肠肝病学
CiteScore
6.40
自引率
3.20%
发文量
420
审稿时长
1 months
期刊介绍: Digestive Diseases and Sciences publishes high-quality, peer-reviewed, original papers addressing aspects of basic/translational and clinical research in gastroenterology, hepatology, and related fields. This well-illustrated journal features comprehensive coverage of basic pathophysiology, new technological advances, and clinical breakthroughs; insights from prominent academicians and practitioners concerning new scientific developments and practical medical issues; and discussions focusing on the latest changes in local and worldwide social, economic, and governmental policies that affect the delivery of care within the disciplines of gastroenterology and hepatology.
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