临床神经外科杂志2025,Vol.22Issue(2):166-173,8.DOI:10.3969/j.issn.1672-7770.2025.02.008
MTHFD2对脑胶质母细胞瘤细胞生长和转移的作用和机制研究
Effect and mechanism of MTHFD2 on the growth and metastasis of glioblastoma cells
摘要
Abstract
Objective To explore the effects of methylenetetrahydrofolate dehydrogenase 2(MTHFD2)on the growth and metastasis of glioblastoma(GBM)cells and its mechanism.Methods The expression level of MTHFD2 in GBM tissues and normal tissues was analyzed by interactive gene expression profile analysis database(GEPIA).U87 MG cells were divided into control group,si-NC group and si-MTHFD2 group.The changes of glycolysis and oxidative stress,as well as cell proliferation,apoptosis,migration and invasion were detected in each group.Xenotransplantation model of nude mice was established and divided into sh-NC group and sh-MTHFD2 group.Tumor volume was measured and tumor growth curve was drawn.The expression levels of MTHFD2 gene were detected by RT-qPCR,and the expression levels of glycolysis key enzymes and epithelial-mesenchymal transition marker proteins were detected by Western blot.Results GEPIA database analysis showed that MTHFD2 was highly expressed in GBM tissues(P<0.05).Compared with normal NHA cells,the relative expression levels of MTHFD2 mRNA and protein in U87 MG cells were increased(P<0.05).Silence of MTHFD2 inhibited the relative glucose intake and lactate production of U87 MG cells,inhibited clone formation,cell proliferation activity,cell migration and invasion,and promoted the level of oxidative stress and cell apoptosis.In the tumor formation experiment of nude mice,silence of MTHFD2 inhibited tumor growth.Conclusions MTHFD2 is a promoter of malignant progression of GBM.The silencing of MTHFD2 expression can effectively inhibit cellular glycolysis stress,suppress cell proliferation,migration,invasion,and tumorigenesis in vivo,while also enhancing oxidative stress and apoptosis.关键词
脑胶质母细胞瘤/亚甲基四氢叶酸脱氢酶2/糖酵解/氧化应激/增殖和凋亡/迁移和侵袭Key words
glioblastoma/methylenetetrahydrofolate dehydrogenase 2/glycolysis/oxidative stress/proliferation and apoptosis/migration and invasion分类
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张亮,李菲,张凌雪,蒋小兵,赵海康..MTHFD2对脑胶质母细胞瘤细胞生长和转移的作用和机制研究[J].临床神经外科杂志,2025,22(2):166-173,8.基金项目
陕西省博士后科研工作站和企业项目资助(2023BSHGZZHQYXMZZ07) (2023BSHGZZHQYXMZZ07)