USP41 regulates glioma malignancy through Notch1 activation: Insights from in vitro and in vivo studies

Background: Glioma is the most prevalent and lethal primary adult central nervous system tumor, with limited therapeutic advances despite extensive research. The ubiquitin-proteasome system (UPS), particularly ubiquitin-specific proteases (USPs), plays critical roles in tumorigenesis. USP41, a member of the USP family, is implicated in multiple Cancer types, but its function in glioma remains poorly understood. This study aimed to investigate the expression, biological functions, and underlying molecular mechanisms of USP41 in glioma cells and tissues, providing insights for targeted therapies.

Methods: USP41 expression levels were examined in clinical glioma specimens, normal brain tissues, and cell lines using qPCR and Western blotting. Bioinformatics analysis was conducted using the GEPIA database and KEGG enrichment to identify related signaling pathways. Functional assays, including CCK-8, EdU, colony formation, Transwell migration/invasion, wound healing, flow cytometry, and a xenograft model, were employed to evaluate proliferation, migration, invasion, Apoptosis, and tumor growth. The role of Notch1 signaling in USP41-mediated glioma regulation was assessed through pharmacological activation (Jagged-1).

Results: USP41 expression was upregulated in glioma tissues and cell lines and associated with poorer survival. USP41 knockdown significantly inhibited glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while promoting Apoptosis in vitro. In vivo, USP41 knockdown reduced tumor size and weight. Mechanistic studies suggested that USP41 enhances glioma progression via the Notch1 pathway.

Conclusions: USP41 is a key regulator of glioma growth and invasiveness through Notch1 signaling. Targeting USP41 may represent a promising therapeutic strategy for improving glioma outcomes.

EMT; Glioma; Notch1 signaling; Proliferation; USP41.