Glioblastoma (GBM) is a WHO grade 4 tumor and is the most malignant form of glioma. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme involved in folate metabolism, has been reported to be highly expressed in several human tumors. However, little is known about the role of MTHFD2 in GBM. In this study, we aimed to explore the biological functions of MTHFD2 in GBM and identify the associated mechanisms. We performed experiments such as immunohistochemistry, Western blot, and transwell assays and found that MTHFD2 expression was lower in high-grade glioma than in low-grade glioma. Furthermore, a high expression of MTHFD2 was associated with a favorable prognosis, and MTHFD2 levels showed good prognostic accuracy for glioma patients. The overexpression of MTHFD2 could inhibit the migration, invasion, and proliferation of GBM cells, whereas its knockdown induced the opposite effect. Mechanistically, our findings revealed that MTHFD2 suppressed GBM progression independent of its enzymatic activity, likely by inducing cytoskeletal remodeling through the regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, thereby influencing GBM malignance. Collectively, these findings uncover a potential tumor-suppressor role of MTHFD2 in GBM cells. MTHFD2 may act as a promising diagnostic and therapeutic target for GBM treatment.

中文翻译：

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MTHFD2 通过抑制 ERK1/2 磷酸化来抑制胶质母细胞瘤的进展。

胶质母细胞瘤 (GBM) 是 WHO 4 级肿瘤，是恶性程度最高的神经胶质瘤。据报道，亚甲基四氢叶酸脱氢酶 2 (MTHFD2) 是一种参与叶酸代谢的线粒体酶，在多种人类肿瘤中高表达。然而，关于 MTHFD2 在 GBM 中的作用知之甚少。在这项研究中，我们旨在探索 MTHFD2 在 GBM 中的生物学功能并确定相关机制。我们进行了免疫组织化学、Western blot 和 transwell 分析等实验，发现 MTHFD2 在高级别胶质瘤中的表达低于低级别胶质瘤。此外，MTHFD2 的高表达与良好的预后相关，并且 MTHFD2 水平对神经胶质瘤患者具有良好的预后准确性。MTHFD2的过表达可以抑制迁移、侵袭、和 GBM 细胞的增殖，而其敲低引起相反的效果。从机制上讲，我们的研究结果表明，MTHFD2 抑制 GBM 进展与其酶活性无关，可能是通过调节细胞外信号调节激酶 1/2 (ERK1/2) 磷酸化诱导细胞骨架重塑，从而影响 GBM 恶性程度。总的来说，这些发现揭示了 MTHFD2 在 GBM 细胞中的潜在肿瘤抑制作用。MTHFD2 可能作为 GBM 治疗的有前途的诊断和治疗靶点。可能通过调节细胞外信号调节激酶 1/2 (ERK1/2) 磷酸化诱导细胞骨架重塑，从而影响 GBM 恶性程度。总的来说，这些发现揭示了 MTHFD2 在 GBM 细胞中的潜在肿瘤抑制作用。MTHFD2 可能作为 GBM 治疗的有前途的诊断和治疗靶点。可能通过调节细胞外信号调节激酶 1/2 (ERK1/2) 磷酸化诱导细胞骨架重塑，从而影响 GBM 恶性程度。总的来说，这些发现揭示了 MTHFD2 在 GBM 细胞中的潜在肿瘤抑制作用。MTHFD2 可能作为 GBM 治疗的有前途的诊断和治疗靶点。