Transcription factor NFKB1 mediates TUBB6 to promote the proliferation and suppress apoptosis in glioma via Wnt/β-catenin signaling pathway.

Abstract

Glioma remains one of the most challenging brain tumors with poor prognosis. In this study, we aimed to elucidate the role of TUBB6 in glioma and its potential as a diagnostic and prognostic biomarker. Analysis of the GSE42656 and TCGA datasets revealed that TUBB6 was significantly upregulated in glioma tissues compared to normal tissues. The diagnostic value of TUBB6 was demonstrated with an area under the curve (AUC) of 0.702, suggesting that it could be used as a biomarker to differentiate gliomas Correlation analyses revealed that high TUBB6 expressions were associated with advanced WHO grades, IDH mutation status, and histological types of glioma. Further investigation identified NFKB1 as a key transcription factor that binds to the promoter region of TUBB6, upregulating its expression in glioma cells. Elevated levels of NFKB1 were associated with poor overall survival and disease-specific survival in glioma patients. Knockdown of NFKB1 resulted in reduced TUBB6 expression in glioma cells, confirming the regulatory roles of NFKB1 in TUBB6 expression. Prognostic analysis using TCGA and CGGA datasets demonstrated that high TUBB6 expression was associated with poorer overall survival (OS) and disease-specific survival (DSS) in glioma patients. TUBB6 was identified as an independent prognostic factor for both OS and DSS. Additionally, pan-cancer analysis revealed that TUBB6 was dysregulated in various tumor types and showed prognostic value across multiple cancers. Functional enrichment analysis of TUBB6-associated differentially expressed genes indicated involvement in immune response, extracellular matrix remodeling, and cytokine signaling pathways. In vitro experiments showed that TUBB6 knockdown suppressed glioma cell proliferation and promoted apoptosis by regulating the canonical Wnt/β-catenin signaling pathway. Our findings suggest that TUBB6 contributes to glioma malignancy through its effects on the Wnt/β-catenin pathway. In conclusion, TUBB6 emerges as a promising biomarker for glioma diagnosis and prognosis. Its regulation by NFKB1 and involvement in key signaling pathways underscore its potential as a therapeutic target for glioma treatment.