HNRNPAB drives glioblastoma proliferation by stabilizing EZH2 mRNA

Background Glioblastoma (GBM) is the most lethal primary brain tumor, characterized by profound therapeutic resistance to both radiotherapy and chemotherapy, resulting in universally dismal prognoses. Although aberrant RNA metabolism and post-transcriptional regulation are increasingly implicated in tumorigenesis, the functional contributions of heterogeneous nuclear ribonucleoproteins (HNRNPs) in GBM progression remain largely unexplored. Specifically, the regulatory network connecting HNRNP family members to oncogenic epigenetic modifications and downstream proliferative signaling is poorly understood. Moreover, reliable prognostic biomarkers for risk stratification and targeted intervention are still urgently needed. In this study, we investigated the clinical significance, biological functions, and molecular mechanisms of HNRNPAB in glioblastoma to identify novel therapeutic vulnerabilities and prognostic indicators. Results Integrated bioinformatic analysis of TCGA and CGGA cohorts identified five HNRNP family genes as independent prognostic risk factors, with HNRNPAB markedly upregulated in high-grade and IDH-wildtype gliomas, correlating with poor survival. Functional assays showed that HNRNPAB knockdown suppressed proliferation, induced G1 arrest, and impaired orthotopic tumor growth. Mechanistically, HNRNPAB directly bound and stabilized EZH2 mRNA, enhancing EZH2 expression and H3K27me3 modification, which activated PI3K-AKT-mTOR and ERK signaling. Critically, rescue experiments demonstrated that HNRNPAB overexpression in HNRNPAB-knockdown U251 cells effectively restored EZH2 expression and rescued cellular proliferative capacity, confirming that HNRNPAB drives glioblastoma progression specifically through the EZH2-dependent axis. Conclusion Our study identifies the HNRNPAB–EZH2 axis as a potential driver of glioblastoma progression, in which HNRNPAB stabilizes EZH2 mRNA to activate oncogenic signaling. This axis may serve as a prognostic biomarker and a candidate therapeutic target warranting further validation in IDH-wildtype glioblastoma.