Identification of the Oncogenic Role of MSH2 in the Stemness and Progression of Glioma Through Regulating Wnt Signaling Pathway

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-06-30 DOI:10.1002/cam4.70993

Jun Liu, Jiayu Chen, Lianglei Jiang

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Abstract

Background

Glioma is one of the most aggressive brain tumors, and its progression is often associated with stemness maintenance and therapy resistance. The role of MSH2 in glioma remains largely unclear.

Methods

We analyzed public datasets and clinical samples to assess MSH2 expression and its clinical relevance. Functional assays in vitro and in vivo were performed to investigate the effects of MSH2 knockdown on glioma cell behavior. Mechanistic studies were conducted to explore downstream signaling pathways and stemness regulation.

Results

MSH2 was found to be significantly upregulated in glioma tissues and cell lines, and its high expression correlated with poor prognosis. Silencing MSH2 inhibited cell proliferation, migration, and tumor growth, while promoting apoptosis and G2 cell cycle arrest. Mechanistically, phospho-kinase screening and rescue experiments suggested that MSH2 promotes glioma progression via activation of the Wnt/β-catenin signaling pathway. Furthermore, MSH2 knockdown suppressed the expression of stemness markers, impaired sphere formation, and sensitized glioma cells to cisplatin treatment.

Conclusions

Our study identifies MSH2 as an oncogenic factor in glioma, which drives stemness and progression through regulation of the Wnt/β-catenin pathway, and may serve as a potential therapeutic target.

Abstract Image

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MSH2通过调控Wnt信号通路在胶质瘤发生发展中的致癌作用

神经胶质瘤是最具侵袭性的脑肿瘤之一，其进展通常与干细胞维持和治疗抵抗有关。MSH2在胶质瘤中的作用仍不清楚。方法分析公共数据集和临床样本，评估MSH2表达及其临床相关性。通过体外和体内功能实验研究MSH2敲除对胶质瘤细胞行为的影响。通过机制研究来探索下游信号通路和干性调控。结果MSH2在胶质瘤组织和细胞系中表达显著上调，其高表达与预后不良相关。沉默MSH2抑制细胞增殖、迁移和肿瘤生长，同时促进细胞凋亡和G2细胞周期阻滞。从机制上讲，磷酸激酶筛选和救援实验表明MSH2通过激活Wnt/β-catenin信号通路促进胶质瘤的进展。此外，MSH2敲低抑制了干细胞标记物的表达，破坏了球的形成，并使胶质瘤细胞对顺铂治疗敏感。结论本研究确定MSH2是胶质瘤的一个致癌因子，它通过调控Wnt/β-catenin通路驱动胶质瘤的发生和进展，可能是一个潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.