USP18 deubiquitinates and stabilizes SOX9 to promote the stemness and malignant progression of glioblastoma by Zhiyuan Liu & Kuo Yu & Kaile Chen & Yi Zhang & Kexiang Dai & Liang Zhao & Peng Zhao instant download

USP18 deubiquitinates and stabilizes SOX9 to promote the stemness and malignant progression of glioblastoma by Zhiyuan Liu & Kuo Yu & Kaile Chen & Yi Zhang & Kexiang Dai & Liang Zhao & Peng Zhao instant download

Glioblastoma (GBM), the most common and aggressive primary brain tumour, is associated with poor prognosis, primarily due to itsstem-like subpopulation, glioblastoma stem cells (GSCs). The deubiquitinase (DUB) family has attracted an increasing amount ofattention due to its roles in GSC biology and tumour aggressiveness. In this study, we focused on ubiquitin-specific peptidase 18(USP18), a member of the DUB family whose role in GBM is poorly understood. Through integrated bioinformatics analyses andexperimental investigations using patient-derived samples, cell models, and animal models, we elucidated the role of USP18 inenhancing GSC stemness and promoting malignant behaviours. Our findings revealed that USP18 expression is significantlyelevated in GBM and is correlated with a poor prognosis. Mechanistically, USP18 interacts with SRY-box transcription factor 9(SOX9), stabilising its protein levels by cleaving K48-linked polyubiquitin chains. Additionally, we identified YY1 as a transcriptional1234567890();,:regulator of USP18, increasing its expression in GBM cells. These findings reveal that USP18 is a potential therapeutic targethighlight the novel YY1/USP18/SOX9 signalling axis implicated in GBM progression.Cell Death Discovery (2025) 11:237 ;