Chen Shenbo, Yang Liangwang, Li Zhengzheng, Zhuo Shenghua, Yan Bo, Zhang Zhaoteng, Zhang Jinben, Feng Haizhong, Yang Kun
Department of Neurosurgery, The Affiliated Hospital of Hainan Medical College Haikou 570102, Hainan, China.
State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200127, China.
Am J Transl Res. 2021 Jun 15;13(6):6055-6065. eCollection 2021.
EGFR/EGFR variant III (EGFRvIII) glioblastoma is seriously malignant, and the underlying mechanism remains unclear. In this study, EGFR and GLUT3 were found to be co-expressed in our collected tissues and associated with worse overall survival in glioblastoma via bioinformatics analysis. Functionally, and tests revealed that silencing GLUT3 substantially inhibited the viability of U87-EGFRvIII and LN229-EGFRvIII cells. Compared with wild-type U87 or LN229 cells, the expression level of SOX9 in U87-EGFRvIII or LN229-EGFRvIII cells (U87 and LN229 over-expressing EGFRvIII) was substantially increased. Chromatin immunoprecipitation and Dual-luciferase reporter assays revealed that SOX9 bound to the promoter of GLUT3 and promoted the expression of GLUT3. Collectively, our findings indicated that the EGFR/EGFRvIII-SOX9-GLUT3 axis mediated the tumourigenesis of glioblastoma and might be a potential target for glioblastoma therapy.
表皮生长因子受体/表皮生长因子受体III型变异体（EGFRvIII）胶质母细胞瘤具有高度恶性，其潜在机制尚不清楚。在本研究中，通过生物信息学分析发现，在我们收集的组织中，EGFR和葡萄糖转运蛋白3（GLUT3）共同表达，且与胶质母细胞瘤患者较差的总生存期相关。在功能方面，实验表明，沉默GLUT3可显著抑制U87-EGFRvIII和LN229-EGFRvIII细胞的活力。与野生型U87或LN229细胞相比，U87-EGFRvIII或LN229-EGFRvIII细胞（过表达EGFRvIII的U87和LN229细胞）中SOX9的表达水平显著升高。染色质免疫沉淀和双荧光素酶报告基因检测表明，SOX9与GLUT3启动子结合并促进GLUT3的表达。总之，我们的研究结果表明，EGFR/EGFRvIII-SOX9-GLUT3轴介导了胶质母细胞瘤的肿瘤发生，可能是胶质母细胞瘤治疗的潜在靶点。
