NTAN1 Promotes Glioblastoma Malignant Progression and Is a Novel Prognostic Factor of Poor Prognosis

Background/Objectives: Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor, and elucidating the molecular determinants of its malignant progression is essential for improving patient outcomes. NTAN1 encodes N-terminal asparagine amidase 1, a component of the N-degron pathway involved in selective protein turnover; however, its role in GBM remains unclear. This study aimed to investigate the clinical significance and biological function of NTAN1 in GBM. Methods: Integrated analyses of The Cancer Genome Atlas (TCGA) transcriptomic and clinical data were performed, together with tissue microarray validation, to assess the association between NTAN1 expression and prognosis in GBM. Immunohistochemical analysis of GBM specimens was conducted to evaluate NTAN1 protein expression. Functional studies, including NTAN1 knockdown and overexpression experiments, were used to examine its effects on GBM cell proliferation, clonogenic growth, migration, and invasion. An orthotopic GBM model was established to assess the effect of NTAN1 inhibition on tumor growth. Transcriptomic analysis was further performed to explore the molecular changes associated with NTAN1 knockdown. Results: Elevated NTAN1 expression was associated with poor survival in GBM. Immunohistochemical analysis further demonstrated that high NTAN1 protein expression predicted unfavorable prognosis. Functional studies showed that NTAN1 knockdown inhibited GBM cell proliferation, clonogenic growth, migration, and invasion, whereas NTAN1 overexpression promoted these malignant phenotypes. In an orthotopic GBM model, NTAN1 inhibition significantly reduced tumor volume. Transcriptomic analysis showed that NTAN1 knockdown was associated with reduced expression of invasion-related genes, including SPINK1, MMP1, and LIF, and with enrichment changes in inflammation-associated pathways, suggesting that NTAN1 may promote GBM progression through pro-invasive molecular programs. Conclusions: Collectively, these findings identify NTAN1 as a potential promoter of GBM malignant progression and a prognostic biomarker of poor outcome.