PSMA5 as a modulator of glioblastoma senescence and prognosis.

OBJECTIVE: The present study aimed to construct a tumor risk prognosis model and explore the role of PSMA5 in glioblastoma (GBM), focusing on its association with cellular senescence and its potential as both a prognostic biomarker and therapeutic target. METHODS: Data from the DepMap and Cellage databases were integrated to develop a risk prognosis model, and were refined and evaluated using LASSO and Cox regression analyses. PSMA5 expression in GBM was analyzed via bioinformatics methods and validated in cell lines. Functional experiments using U87 and U251 cells subjected to PSMA5 overexpression and knockdown were conducted to assess changes in proliferation, senescence, cell cycle, DNA damage and associated protein expression. Additionally, a subcutaneous tumor model in immunodeficient mice was used to evaluate tumor growth and analyze tissue characteristics. RESULTS: The model identified 5 key genes and demonstrated strong predictive accuracy, with high-risk patients exhibiting significantly shorter survival times. PSMA5 expression was notably elevated in GBM tissues and cell lines compared with normal controls and associated with clinical features. Functional assays revealed that PSMA5 regulates GBM cell proliferation, invasion and migration, while its knockdown induced cellular senescence, characterized by increased β-galactosidase activity, disrupted cell cycle progression and DNA damage. In vivo studies confirmed that PSMA5 overexpression significantly accelerated tumor growth and was widely distributed within tumor tissues. CONCLUSION: The proposed model is reliable, and PSMA5 plays a critical role in GBM progression by influencing tumor cell behavior and promoting growth. As both a prognostic biomarker and a therapeutic target, PSMA5 offers valuable insights for advancing GBM research and treatment strategies.