KIF4A promotes epithelial-mesenchymal transition by activating the TGF-β/SMAD signaling pathway in glioma cells.

IF 3.5 2区生物学 Q3 CELL BIOLOGY

Molecular and Cellular Biochemistry Pub Date : 2025-01-01 Epub Date: 2024-02-27 DOI:10.1007/s11010-024-04943-z

Yao Xu, Guangren Xue, Lei Zhou, Gaotian Wu, Lingji Hu, Shuchen Ma, Jian Zhang, Xiangdong Li

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Abstract

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.

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KIF4A 通过激活胶质瘤细胞中的 TGF-β/SMAD 信号通路促进上皮-间质转化。

胶质瘤是最常见的原发性脑肿瘤，据报道，高级别胶质瘤患者的预后较差。驱动蛋白家族成员 4 A（KIF4A）能刺激肿瘤细胞的增殖、迁移和侵袭。然而，它在胶质瘤中的功能尚未得到明确证实。因此，本研究旨在探讨 KIF4A 对胶质瘤细胞上皮-间质转化和侵袭的影响。我们检索了癌症基因组图谱和中国胶质瘤基因组图谱数据库，以确定与KIF4A相关的信号通路和下游基因。我们还在 U251 和 U87 人类胶质母细胞瘤细胞中使用 Western 印迹、transwell 迁移和侵袭、伤口愈合划痕和双荧光素酶报告实验进一步验证了它们。我们对癌症基因组图谱（Cancer Genome Atlas）和中国胶质瘤基因组图谱（Chinese Glioma Genome Atlas）数据的分析表明，胶质瘤患者的 KIF4A 表达升高，且与临床分级相关。在这里，KIF4A的过表达促进了胶质瘤细胞的迁移、侵袭和增殖，而KIF4A的敲除则显示了相反的结果。基因本体（GO）和基因组富集分析（GSEA）表明，KIF4A能积极控制胶质瘤细胞中的TGF-β/SMAD信号转导。此外，遗传相关性分析表明，KIF4A 转录控制着苯并咪唑-1 在胶质瘤细胞中的表达。KIF4A通过苯并咪唑-1调节胶质瘤细胞中的TGF-β/SMAD信号通路，从而促进上皮-间质转化。

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

Molecular and Cellular Biochemistry 生物-细胞生物学

CiteScore

8.30

自引率

2.30%

发文量

293

审稿时长

1.7 months

期刊介绍： Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.