Xu Yao, Xue Guangren, Zhou Lei, Wu Gaotian, Hu Lingji, Ma Shuchen, Zhang Jian, Li Xiangdong
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Neurosurgery, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China.
Mol Cell Biochem. 2025 Jan;480(1):217-230. doi: 10.1007/s11010-024-04943-z. Epub 2024 Feb 27.
Gliomas are the most prevalent type of primary brain tumor, with poor prognosis reported in patients with high-grade glioma. Kinesin family member 4 A (KIF4A) stimulates the proliferation, migration, and invasion of tumor cells. However, its function in gliomas has not been clearly established. Therefore, this study aimed to investigate the effects of KIF4A on the epithelial-mesenchymal transition and invasion of glioma cells. We searched The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases to identify KIF4A-related signaling pathways and downstream genes. We further validated them using western blotting, transwell migration and invasion, wound-healing scratch, and dual-luciferase reporter assays in U251 and U87 human glioblastoma cells. Our analysis of the Cancer Genome Atlas and Chinese Glioma Genome Atlas data showed elevated KIF4A expression in patients with gliomas and was associated with clinical grade. Here, KIF4A overexpression promoted the migration, invasion, and proliferation of glioma cells, whereas KIF4A knockdown showed contrasting results. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) analyses demonstrated that KIF4A positively controls TGF-β/SMAD signaling in glioma cells. Additionally, genetic correlation analysis revealed that KIF4A transcriptionally controls benzimidazoles-1 expression in glioma cells. KIF4A promotes the epithelial-mesenchymal transition by regulating the TGF-β/SMAD signaling pathway via benzimidazoles-1 in glioma cells.
神经胶质瘤是最常见的原发性脑肿瘤类型，高级别神经胶质瘤患者的预后较差。驱动蛋白家族成员4A（KIF4A）可刺激肿瘤细胞的增殖、迁移和侵袭。然而，其在神经胶质瘤中的功能尚未明确。因此，本研究旨在探讨KIF4A对神经胶质瘤细胞上皮-间质转化和侵袭的影响。我们检索了癌症基因组图谱（The Cancer Genome Atlas）和中国神经胶质瘤基因组图谱（Chinese Glioma Genome Atlas）数据库，以确定与KIF4A相关的信号通路和下游基因。我们进一步在U251和U87人胶质母细胞瘤细胞中，通过蛋白质免疫印迹法、Transwell迁移和侵袭实验、伤口愈合划痕实验以及双荧光素酶报告基因检测对其进行了验证。我们对癌症基因组图谱和中国神经胶质瘤基因组图谱数据的分析显示，神经胶质瘤患者中KIF4A表达升高，且与临床分级相关。在此，KIF4A过表达促进了神经胶质瘤细胞的迁移、侵袭和增殖，而KIF4A基因敲低则显示出相反的结果。基因本体论（GO）和基因集富集分析（GSEA）表明，KIF4A在神经胶质瘤细胞中正向调控转化生长因子-β（TGF-β）/SMAD信号通路。此外，遗传相关性分析显示，KIF4A在转录水平上调控神经胶质瘤细胞中苯并咪唑-1的表达。在神经胶质瘤细胞中，KIF4A通过苯并咪唑-1调节TGF-β/SMAD信号通路，从而促进上皮-间质转化。
