Qiao Yang, Zhou Lv, Nie Jianyu, Li Jinshui, Hu Yangchun, Gao Peng, Wu Bingshan, Cheng Hongwei, Dai Xingliang
Department of Neurosurgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230001, China.
Department of Clinical Medicine, the Second Clinical College of Anhui Medical University, Hefei, Anhui, 230032, China.
Mol Biomed. 2025 Jun 5;6(1):35. doi: 10.1186/s43556-025-00274-7.
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.
胶质母细胞瘤（GBM）具有高度恶性，预后较差。探索GBM新的治疗靶点是改善GBM患者预后的有效策略。已发现跨膜含emp24结构域蛋白3（TMED3）基因在多种癌症的发生发展中发挥作用，但其在GBM中的作用机制尚不清楚。本研究结合TCGA数据库、单细胞RNA测序以及体外和体内实验，系统地研究了TMED3在GBM中的作用及其潜在机制。研究发现，TMED3基因在GBM样本中存在差异表达，高表达与更高分级的GBM和更差的预后相关。体外和体内实验证实，TMED3的上调促进了GBM的增殖、侵袭和迁移。进一步的免疫沉淀和功能挽救实验表明，含锌指和BTB结构域蛋白7A（ZBTB7A）是TMED3的下游靶点。TMED3通过调节ZBTB7A促进GBM的恶性进展。总之，本研究揭示了TMED3通过调节ZBTB7A信号轴促进GBM的发展，为GBM的靶向治疗提供了新的见解。
