WTAP Promotes Malignant Progression and Immune Escape of Glioblastoma by Regulating N6-methyladenosine Modification of CENPF

Glioblastoma (GBM) is a malignant tumor. It has been shown that centromere protein F (CENPF) may serve as a potential prognostic biomarker for glioma patients, while Wilms' tumor 1-associating protein (WTAP) is frequently upregulated across various cancers. However, the specific roles of CENPF and WTAP in GBM remain largely undefined. The differently expressed genes in GBM and expression levels of CENPF and WTAP were analyzed using bioinformatics analysis. The gene expression was examined using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The cell counting kit-8 (CCK8), flow cytometry, transwell, and wound healing assays were used to detect cell viability, apoptosis, invasion, and migration, respectively. The volume and weight of xenograft tumors in mice were detected, and Ki-67, Cleaved caspase-3, and CENPF levels were examined by immunohistochemistry (IHC) assays. CD8⁺ T cell proliferation and apoptosis were examined by immunofluorescence (IF) and terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL), respectively. RMBase v3.0 website was used to predict the N6-methyladenosine (m6A) methylation modification sites of CENPF. The relationship between WTAP and CENPF was analyzed using the RNA-protein binding sites prediction (RBP) website and RNA immunoprecipitation (RIP) assay. Additionally, the m6A methylation levels of CENPF were detected using methylated RNA immunoprecipitation (Me-RIP). In GBM cells and tissues, CENPF expression was increased. Furthermore, CENPF promoted cell viability, invasion, and migration, and inhibited apoptosis and CD8⁺ T cell immunity in GBM. In vivo, CENPF promoted the growth of mice tumors. Mechanistically, WTAP regulated the expression of CENPF via m6A modification. Moreover, WTAP facilitated GBM progression and immune escape through upregulating CENPF. Together, WTAP promotes cell malignant progression and immune escape in GBM through regulating m6A modification of CENPF. These findings may provide a novel theoretical basis for the treatment of GBM.