异常WDR5通过YAP1- CTGF途径促进宫颈癌的进展

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-05-23 DOI:10.1016/j.lfs.2025.123712

Xiaofeng Ma , Zhonglei Xu , Xinrui Wang , Shiying Sun , Junhui Zhang , Ruxian Tang , Lin Ling , Bing Wei , Liangchang Hu , Enlin Wang

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引用次数: 0

摘要

AimsWDR5在促进各种恶性肿瘤的癌症进展中起关键作用。然而，它与子宫颈癌的关系仍然知之甚少。本研究旨在阐明WDR5驱动宫颈癌进展的机制。材料与方法分析宫颈癌组织中WDR5的调控情况。体外实验评估了WDR5功能丧失对细胞增殖、迁移和侵袭的影响。机制研究探讨了WDR5和YAP1之间的相互作用，以及随后通过组蛋白3赖氨酸4三甲基化对CTGF基因表达的调节。利用异种移植肿瘤模型来检测WDR5在宫颈癌进展中的体内作用。关键发现swdr5在宫颈癌组织中显著上调，并与预后不良相关。在体外实验中，WDR5功能的缺失明显抑制宫颈癌细胞的增殖、迁移和侵袭。WDR5与YAP1相互作用，通过组蛋白甲基化增强CTGF表达。在体内，WDR5的致癌功能取决于YAP1-CTGF信号轴。本研究确定WDR5/YAP1/CTGF通路是宫颈癌进展的关键机制，提示靶向该轴可能提供一种有前景的治疗方法。

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Aberrant WDR5 promotes the progression of cervical cancer through the YAP1- CTGF pathway

Aims

WDR5 plays a pivotal role in promoting cancer progression across various malignancies. However, its involvement in cervical cancer remains poorly understood. This study aims to elucidate the mechanisms by which WDR5 drives cervical cancer progression.

Materials and methods

Cervical cancer tissues were analyzed to assess WDR5 regulation. In vitro assays evaluated the effects of WDR5 loss-of-function on cell proliferation, migration, and invasion. Mechanistic studies investigated the interaction between WDR5 and YAP1, and the subsequent modulation of CTGF gene expression via histone 3 lysine 4 trimethylation. Xenograft tumor models were utilized to examine the in vivo role of WDR5 in cervical cancer progression.

Key findings

WDR5 is significantly upregulated in cervical cancer tissues and correlates with poor prognosis. Loss of WDR5 function markedly suppresses cervical cancer cell proliferation, migration, and invasion in vitro. WDR5 interacts with YAP1, enhancing CTGF expression through histone methylation. In vivo, the oncogenic function of WDR5 is contingent upon the YAP1-CTGF signaling axis.

Significance

This study identifies the WDR5/YAP1/CTGF pathway as a key mechanism in cervical cancer progression, suggesting that targeting this axis may provide a promising therapeutic approach.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.