Unraveling the role of PBK in glioblastoma: from molecular mechanisms to therapeutic targets.

Abstract

Background: This study investigates the gene expression characteristics of glioma-initiating cells (GIC), an important subgroup of glioblastoma (GBM), after knockdown of PBK (PDZ-binding kinase). Differentially expressed genes (DEGs) between PBK knockdown GIC and control groups were screened through bioinformatics methods. The authors analyzed the mechanisms and roles of these DEGs in GBM tumorigenesis and patient prognosis.

Methods: Microarray data (GSE53800) were obtained from the Gene Expression Omnibus (GEO) database, selecting 18 GIC cell line samples with or without PBK knockdown. Each control and knockdown group contained three samples. DEGs were screened using R software. GO enrichment analysis, KEGG pathway analysis, PPI network analysis, and hub gene identification were conducted to explore DEG mechanisms. Western blot analysis was also performed to detect EIF4E protein expression, one of the key hub genes, after PBK knockdown in the HS683 glioma cell line.

Results: A total of 175 upregulated and 145 downregulated genes were identified. GO analysis showed that DEGs were mainly enriched in the positive regulation of cell proliferation, cell adhesion, and angiogenesis. KEGG pathway analysis revealed that DEGs were mainly involved in neuroactive ligand-receptor interactions, calcium signaling, and HIF-1 signaling pathways. Western blot results indicated that EIF4E was downregulated after PBK knockdown.

Conclusion: A group of genes, such as EIF4E, were closely associated with PBK expression and functions. These findings may provide insight into the molecular mechanism of PBK in GBM.