Zhou Peng, Wei Qianfeng, Wang Haoqian, Yu Tao, Chen Lin, Huang Qiliang, Wei Li, Jiang Jingting
Department of Neurosurgery, The Third Affliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
Department of Orthopedics, Zhenglu town Central Hospital of Tianning District, Changzhou, Jiangsu Province, China.
Sci Rep. 2025 Jul 23;15(1):26781. doi: 10.1038/s41598-025-09167-9.
RUNX2, a member of the RUNX transcription factor family, has been reported to promote epithelial-mesenchymal transition (EMT) in various malignancies, yet its role in glioma remains poorly understood. In this study, we systematically analyzed RUNX2 expression and clinical relevance in glioma using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets via the UALCAN web portal. Kaplan-Meier survival analyses and Wilcoxon rank-sum tests were employed to assess the prognostic significance of RUNX2. We further validated RUNX2 expression in glioma tissues and cell lines using RT-qPCR and Western blotting. Functional experiments, including CCK-8, wound healing, transwell invasion, and apoptosis assays, were conducted in U251 glioma cells with RUNX2 knockdown via siRNA. EMT-related proteins and components of the TGF-β/Smad pathway were examined by Western blot. In addition, we employed multiplex immunohistochemistry on 160 glioma specimens to analyze the spatial relationship between RUNX2 and EMT markers. Our results demonstrate that RUNX2 is significantly upregulated in glioma tissues and correlates with higher tumor grade, IDH-wildtype status, and poorer overall and disease-free survival. RUNX2 knockdown significantly inhibited glioma cell proliferation, migration, and invasion, while promoting apoptosis. Mechanistically, RUNX2 modulated the expression of EMT markers and activated the TGF-β1/Smad2/3 signaling axis. Collectively, our findings suggest that RUNX2 promotes EMT and malignant progression in glioma via the TGF-β/Smad pathway, and may serve as a potential therapeutic target and prognostic biomarker.
RUNX2是RUNX转录因子家族的成员之一，据报道它可促进多种恶性肿瘤中的上皮-间质转化（EMT），但其在胶质瘤中的作用仍知之甚少。在本研究中，我们通过UALCAN门户网站，利用癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据集，系统分析了RUNX2在胶质瘤中的表达及其临床相关性。采用Kaplan-Meier生存分析和Wilcoxon秩和检验来评估RUNX2的预后意义。我们进一步通过RT-qPCR和蛋白质免疫印迹法验证了RUNX2在胶质瘤组织和细胞系中的表达。通过小干扰RNA（siRNA）敲低U251胶质瘤细胞中的RUNX2，进行了包括CCK-8、伤口愈合、Transwell侵袭和凋亡检测在内的功能实验。通过蛋白质免疫印迹法检测EMT相关蛋白和TGF-β/Smad信号通路的成分。此外，我们对160例胶质瘤标本进行了多重免疫组化分析，以分析RUNX2与EMT标志物之间的空间关系。我们的结果表明，RUNX2在胶质瘤组织中显著上调，且与更高的肿瘤分级、异柠檬酸脱氢酶（IDH）野生型状态以及更差的总生存期和无病生存期相关。敲低RUNX2可显著抑制胶质瘤细胞的增殖、迁移和侵袭，同时促进细胞凋亡。机制上，RUNX2调节EMT标志物的表达并激活TGF-β1/Smad2/3信号轴。总的来说，我们的研究结果表明，RUNX2通过TGF-β/Smad信号通路促进胶质瘤中的EMT和恶性进展，可能作为潜在的治疗靶点和预后生物标志物。
