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

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.