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SPOPL induces tumorigenicity and stemness in glioma stem cells by activating Notch signaling

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Abstract

Objective

Recent studies have increasingly shown that glioma stem cells (GSCs) are extremely important for developing and treating glioblastoma multiforme (GBM). The Broad-complex, Tram-track, and Bric-a-brac protein family is functionally related to a variety of tumor stem cells, and the role of SPOPL as a member of this family in GSCs deserves to be investigated.

Methods

To investigate the expression of SPOPL in GSCs and its impact on the prognosis of GBM patients by using clinical specimens, patient-derived primary GSCs and public databases. In vivo and in vitro, the effect of SPOPL on the proliferation, self-renewal, and differentiation ability of GSCs was explored. Probing the mechanism by which SPOPL affects the biological function of GSCs using RNA sequencing (RNA-seq) and rescue experiments.

Results

The expression of SPOPL was significantly upregulated in GSCs and GBM, and patients with high SPOPL expression had a poorer prognosis. SPOPL enhanced the proliferation and self-renewal ability of GSCs and enhanced the tumorigenicity of GSCs. The Notch signaling pathway was significantly inhibited in SPOPL knockdown GSCs. Activation or inhibition of the Notch signaling pathway rescued changes in the biological function of GSCs caused by altered SPOPL expression.

Conclusion

SPOPL can be used as a potential prognostic biomarker for GBM in clinical work and promotes the proliferation and stemness of GSCs by activating the Notch signaling pathway, which may be a potential molecule for targeting GSCs to treat GBM.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81971663) and the Science and Technology Program Key Project of Guangzhou (Grant No. 201604020004).

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Author notes

  1. Tianyu Hu and Ruoheng Xuan have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Tianyu Hu, Ruoheng Xuan, Erqiao Han, Lingshan Cai & Zhibo Xia

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  1. Tianyu Hu
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Contributions

All authors contributed to the study conception and design. Experimental design and supervision of the article were performed by ZX. The experiments, data analysis, and the first draft of the manuscript were performed by TH, the collection of materials, part of the experiments were performed by RX, the bioinformatics analysis was performed by EH, and part of the animal experiments were performed by CL. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhibo Xia.

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Competing interest

The authors declare no competing interests.

Ethical approval

The study was approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University and conducted by the principles of the Declaration of Helsinki (No. 2020322). The Sun Yat-Sen University’s Institutional Animal Care and Use Committee approved all mice experiments (No. 2021173).

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Hu, T., Xuan, R., Han, E. et al. SPOPL induces tumorigenicity and stemness in glioma stem cells by activating Notch signaling. J Neurooncol 164, 157–170 (2023). https://doi.org/10.1007/s11060-023-04394-4

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  • DOI: https://doi.org/10.1007/s11060-023-04394-4

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