Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
J Neurooncol. 2023 Aug;164(1):157-170. doi: 10.1007/s11060-023-04394-4. Epub 2023 Jul 31.
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.
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.
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.
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.
最近的研究越来越表明，神经胶质瘤干细胞（GSCs）对于多形性胶质母细胞瘤（GBM）的发展和治疗极其重要。Broad-complex、Tram-track 和 Bric-a-brac 蛋白家族在功能上与多种肿瘤干细胞有关，作为该家族成员的 SPOPL 在 GSCs 中的作用值得研究。
通过使用临床标本、患者来源的原代 GSCs 和公共数据库，研究 SPOPL 在 GSCs 中的表达及其对 GBM 患者预后的影响。在体内和体外，探讨 SPOPL 对 GSCs 增殖、自我更新和分化能力的影响。通过 RNA 测序（RNA-seq）和挽救实验探究 SPOPL 影响 GSCs 生物学功能的机制。
SPOPL 在 GSCs 和 GBM 中表达显著上调，高表达 SPOPL 的患者预后较差。SPOPL 增强了 GSCs 的增殖和自我更新能力，并增强了 GSCs 的致瘤性。在 SPOPL 敲低的 GSCs 中，Notch 信号通路显著受到抑制。激活或抑制 Notch 信号通路可挽救因 SPOPL 表达改变而导致的 GSCs 生物学功能的变化。
SPOPL 可作为临床工作中 GBM 的潜在预后生物标志物，通过激活 Notch 信号通路促进 GSCs 的增殖和干性，这可能是一种针对 GSCs 治疗 GBM 的潜在分子。
