F13A1 enhances temozolomide resistance in glioblastoma via activation of the NF-κB signalling pathway

Acquired resistance to temozolomide (TMZ) is a principal driver of therapeutic failure and tumour recurrence in glioblastoma (GBM). This study sought to elucidate the molecular underpinnings of this resistance, aiming to identify viable prognostic markers and therapeutic targets to refine personalized treatment strategies. We integrated gene expression and clinical data from the GEO, TCGA, and CGGA databases. A multipronged approach combining bioinformatics screening with in vitro and in vivo experiments was employed to elucidate the role and mechanism of the candidate gene F13A1 in GBM malignancy and chemoresistance. Our analysis identified F13A1 as a gene whose elevated expression compared with that in lower-grade gliomas or normal tissue strongly correlated with adverse prognosis and higher pathological grade in GBM. The results of functional assays demonstrated that F13A1 knockdown markedly attenuated the proliferative, migratory, and invasive capacities of GBM cells, while they were also resensitized to TMZ. Conversely, F13A1 overexpression resulted in the opposite phenotype, significantly enhancing these malignant traits and increasing TMZ resistance. Mechanistically, pathway enrichment analyses linked F13A1 to epithelial–mesenchymal transition (EMT) and NF-κB signalling. We further established that F13A1 inhibition suppressed both EMT progression and NF-κB pathway activation, thereby counteracting malignant behaviour and drug resistance. Notably, TNF-α stimulation effectively rescued the sh-F13A1-mediated phenotype, confirming the involvement of this pathway. Our findings collectively indicate that F13A1 facilitates GBM aggression and TMZ resistance through the NF-κB-driven induction of EMT. These results suggest that F13A1 is a compelling prognostic biomarker and promising candidate for targeted therapeutic intervention in GBM.