Liu Jun, Chen Jiayu, Jiang Lianglei
Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Department of Neurosurgery, Hubei Provincial Clinical Research Center for Central Nervous System Repair and Functional Reconstruction, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Cancer Med. 2025 Jul;14(13):e70993. doi: 10.1002/cam4.70993.
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.
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.
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.
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.
胶质瘤是最具侵袭性的脑肿瘤之一，其进展通常与干性维持和治疗抵抗相关。MSH2在胶质瘤中的作用仍不清楚。
我们分析了公共数据集和临床样本，以评估MSH2的表达及其临床相关性。进行了体外和体内功能试验，以研究敲低MSH2对胶质瘤细胞行为的影响。开展了机制研究，以探索下游信号通路和干性调节。
发现MSH2在胶质瘤组织和细胞系中显著上调，其高表达与预后不良相关。沉默MSH2可抑制细胞增殖、迁移和肿瘤生长，同时促进细胞凋亡和G2期细胞周期阻滞。机制上，磷酸激酶筛选和挽救实验表明，MSH2通过激活Wnt/β-连环蛋白信号通路促进胶质瘤进展。此外，敲低MSH2可抑制干性标志物的表达，损害球体形成，并使胶质瘤细胞对顺铂治疗敏感。
我们的研究确定MSH2是胶质瘤中的致癌因子，其通过调节Wnt/β-连环蛋白途径驱动干性和进展，并可能作为潜在的治疗靶点。
