Mechanistic study on PSMB9 and HLA-F regulating polyamine metabolism to mediate the malignant progression of glioma

Polyamine metabolism correlates with tumor progression, yet its regulatory networks in glioblastoma multiforme and lower grade glioma (GBMLGG) remain unclear. This study aimed to screen polyamine metabolism related gene (PMRG)-related prognostic biomarkers in glioma malignant progression. First, GBMLGG-ralated datasets were acquired from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Ten core prognostic PMRGs were screened via differential expression and univariate Cox regression, with PSMB9 highly expressed and correlated with adverse clinical features and poor prognosis in both cohorts. PSMB9 overexpression promoted glioma cell malignant phenotypes in vitro while knockdown inhibited them, as verified by Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and Western Blot (WB) in cell lines, and its high expression was associated with abnormal immune infiltration, immune escape, distinct mutation profiles and increased camptothecin sensitivity. Subsequently, HLA-F was confirmed as PSMB9's key downstream gene via Protein-Protein Interaction (PPI) network and Spearman correlation from transcriptome sequencing of knockdown cells, with regulatory relationships verified by functional experiments, and PSMB9 drove glioma malignancy by regulating HLA-F. Finally, in vivo nude mouse assays confirmed PSMB9 knockdown reduced tumor growth, and joint survival analysis showed co-high expression of PSMB9 and downstream genes enhanced poor prognosis prediction. In conclusion, PSMB9 is a novel prognostic biomarker and oncogene in GBMLGG that drives malignancy via HLA-F regulation. The PSMB9-HLA-F axis represents a potential therapeutic target, and their co-expression enhances prognostic prediction.