SPOPL induces tumorigenicity and stemness in glioma stem cells by activating Notch signaling
SPOPL induces tumorigenicity and stemness in glioma stem cells by activating Notch signaling
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DOI：
10.1007/s11060-023-04394-4
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发表时间：
2023-07-31
影响因子：
3.9
通讯作者：
Xia，Zhibo
中科院分区：
文献类型：
--
作者：
Hu，Tianyu;Xuan，Ruoheng;Xia，Zhibo
最近的研究越来越多地表明，胶质瘤干细胞（GSC）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蛋白家族与多种肿瘤干细胞功能相关，SPOPL作为该家族成员在GSCs中的作用值得研究。在体内和体外实验中，研究了SPOPL对GSCs增殖、自我更新和分化能力的影响。通过RNA测序（RNA-seq）和拯救实验（rescue experiments. Results. ResultsSPOPL在GSCs和GBM中表达显著上调，SPOPL高表达患者预后较差。SPOPL能增强GSCs的增殖和自我更新能力，增强GSCs的致瘤性。在SPOPL敲低的GSC中，Notch信号通路被显著抑制。结论SPOPL可作为一种潜在的GBM预后生物标志物用于临床工作，并通过激活Notch信号通路促进GSC的增殖和干细胞化，可能成为靶向GSC治疗GBM的潜在分子。
ObjectiveRecent 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.MethodsTo 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.ResultsThe 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.ConclusionSPOPL 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.