Department of Neurosurgery, The Second Affiliated Hospital, Fujian Medical University, 34# zhongshan North Road, Quanzhou, Fujian, 362000, China.
J Cancer Res Clin Oncol. 2024 Jul 8;150(7):338. doi: 10.1007/s00432-024-05859-3.
Glioma is a leading cause of mortality worldwide, its recurrence poses a major challenge in achieving effective treatment outcomes. Cancer stem cells (CSCs) have emerged as key contributors to tumor relapse and chemotherapy resistance, making them attractive targets for glioma cancer therapy. This study investigated the potential of FERMT1 as a prognostic biomarker and its role in regulating stemness through cell cycle in glioma.
Using data from TCGA-GBM, GSE4290, GSE50161 and GSE147352 for analysis of FERMT1 expression in glioma tissues. Then, the effects of FERMT1 knockdown on cell cycle, proliferation, sphere formation ability, invasion and migration were investigated. The influences of FERMT1 on expression of glycolysis-related proteins and levels of ATP, glucose, lactate and G6PDH were also explored. Furthermore, the effects of FERMT1 knockdown on cellular metabolism were evidenced.
Significant upregulation of FERMT1 in glioma tissues was observed. Silencing FERMT1 not only affected the cell cycle but also led to a notable reduction in proliferation, invasion and migration. The expression of glycolysis-associated proteins including GLUT1, GLUT3, GLUT4, and SCO2 were reduced by FERMT1 knockdown, resulted in increased ATP and glucose as well as decreased lactic acid and G6PDH levels. FERMT1 knockdown also inhibited cellular metabolism. Moreover, FERMT1 knockdown significantly reduced sphere diameter, along with inhibiting the expression of transcription factors associated with stemness in glioma cells.
These findings demonstrated that FERMT1 could be an ideal target for the advancement of innovative strategies against glioma treatment via modulating cellular process involved in stemness regulation and metabolism.
脑胶质瘤是全球主要的致死病因之一，其复发是实现有效治疗效果的主要挑战。癌症干细胞（CSCs）已成为肿瘤复发和化疗耐药的主要贡献者，使其成为脑胶质瘤癌症治疗的有吸引力的靶点。本研究探讨了 FERMT1 作为预后生物标志物的潜力及其通过细胞周期在脑胶质瘤中调节干性的作用。
使用来自 TCGA-GBM、GSE4290、GSE50161 和 GSE147352 的数据分析脑胶质瘤组织中 FERMT1 的表达。然后，研究了 FERMT1 敲低对细胞周期、增殖、球体形成能力、侵袭和迁移的影响。还探讨了 FERMT1 对糖酵解相关蛋白表达和 ATP、葡萄糖、乳酸和 G6PDH 水平的影响。此外，还证明了 FERMT1 敲低对细胞代谢的影响。
观察到脑胶质瘤组织中 FERMT1 的显著上调。FERMT1 沉默不仅影响细胞周期，还导致增殖、侵袭和迁移显著减少。GLUT1、GLUT3、GLUT4 和 SCO2 等糖酵解相关蛋白的表达被 FERMT1 敲低下调，导致 ATP 和葡萄糖增加，乳酸和 G6PDH 水平降低。FERMT1 敲低还抑制了细胞代谢。此外，FERMT1 敲低显著降低了球体直径，同时抑制了脑胶质瘤细胞中与干性相关的转录因子的表达。
这些发现表明，FERMT1 可以成为通过调节与干性调节和代谢相关的细胞过程来推进脑胶质瘤治疗创新策略的理想靶点。
