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

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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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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request, the TCGA database (https://portal.gdc.cancer.gov/), and the CGGA database (https://www.cgga.org.cn).

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Acknowledgements

We would like to thank Professor Hongtao Zhang for providing access to the Suzhou Key Laboratory for Molecular Cancer Genetics.

Funding

This work was supported by Soochow University Mentorship funding (Grant numbers 22122134 and 23122220).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China

    Yao Xu, Lei Zhou, Jian Zhang & Xiangdong Li

  2. Department of Neurosurgery, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China

    Guangren Xue

  3. Laboratory of Cancer Molecular Genetics, Soochow University, Medical College of Soochow University, Suzhou, China

    Gaotian Wu & Lingji Hu

  4. Department of Rehabilitation Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China

    Shuchen Ma

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Contributions

XL provided experimental funding. YX completed major experiments and wrote the main manuscript text. XL and JZ provided the laboratory methods and supervised the laboratory process. GW and LH assisted with some of the experiments. LZ and SM analyzed experimental data. All authors read and approved the final manuscript.

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Correspondence to Jian Zhang or Xiangdong Li.

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Xu, Y., Xue, G., Zhou, L. et al. KIF4A promotes epithelial–mesenchymal transition by activating the TGF-β/SMAD signaling pathway in glioma cells. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-04943-z

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