Transmembrane emp24 domain-containing protein 3 promotes the malignant progression of glioma by regulating the ZBTB7A signaling axis

Abstract Glioblastoma (GBM) is highly malignant with a poor prognosis. Exploring new therapeutic targets in GBM is an effective strategy for the prognosis of GBM patients. The Transmembrane emp24 domain-containing protein 3 (TMED3) gene has been found to play a role in the development of various cancers, but its mechanism in GBM remains unclear. This study combined the TCGA database, single-cell RNA sequencing, and in vitro and in vivo experiments to systematically investigate the role of TMED3 in GBM and its potential mechanisms. The study found that the TMED3 gene is differentially expressed in GBM samples, and high expression is associated with a higher grade of GBM and a poorer prognosis. In vitro and in vivo experiments confirmed that the upregulation of TMED3 promoted GBM proliferation, invasion, and migration. Further immunoprecipitation and functional rescue experiments revealed that Zinc finger and BTB domain-containing protein 7A (ZBTB7A) acts as a downstream target of TMED3. TMED3 promotes the malignant progression of GBM by regulating ZBTB7A. In conclusion, this study reveals that TMED3 promotes GBM development through the regulation of the ZBTB7A signaling axis, providing new insights for targeted therapy of GBM.