Temozolomide（TMZ）是一种常用的治疗胶质母细胞瘤（GBM）的化疗药物，但获得性药物抵抗限制了其治疗效果。我们通过核转录因子Y亚单位β（NFYB）对癌基因丝氨酸羟甲转移酶2（SHMT2）的调控，研究了GBM细胞中TMZ抵抗和糖酵解的潜在机制。将GBM U251细胞转染NFYB、SHMT2和潜在的NFYB靶标组蛋白去乙酰化酶5（HDAC5）相关载体。使用检测试剂盒测量葡萄糖摄取和乳酸产生。通过CCK-8/菌落形成、抓伤、Transwell和流式细胞仪实验分别检测细胞增殖、迁移、侵袭和凋亡。使用染色质免疫共沉淀和双荧光素酶报告实验分别检测NFYB与HDAC5启动子的结合以及NFYB对HDAC5启动子活性的调控。在GBM U251细胞中，NFYB和HDAC5的表达较低，而SHMT2的表达较高。NFYB的过表达或SHMT2的沉默减少了细胞对葡萄糖的摄取、乳酸的产生、增殖、迁移和侵袭，并增加了细胞凋亡和对TMZ的敏感性。NFYB激活HDAC5抑制了SHMT2的表达。SHMT2的过表达使NFYB过表达对糖酵解和TMZ抵抗的抑制效果无效。因此，NFYB通过对HDAC5/SHMT2轴的作用可能降低GBM的肿瘤形成能力和对TMZ的抵抗。© The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Temozolomide (TMZ) is a commonly used chemotherapeutic agent for glioblastoma (GBM), but acquired drug resistance prevents its therapeutic efficacy. We investigated potential mechanisms underlying TMZ resistance and glycolysis in GBM cells through regulation by nuclear transcription factor Y subunit β (NFYB) of the oncogene serine hydroxymethyltransferase 2 (SHMT2). GBM U251 cells were transfected with NFYB-, SHMT2-, and the potential NFYB target histone deacetylase 5 (HDAC5)-related vectors. Glucose uptake and lactate production were measured with detection kits. CCK-8/colony formation, scratch, Transwell, and flow cytometry assays were performed to detect cell proliferation, migration, invasion, and apoptosis, respectively. The binding of NFYB to the HDAC5 promoter and the regulation of NFYB on HDAC5 promoter activity were detected with chromatin immunoprecipitation and dual-luciferase reporter assays, respectively. NFYB and HDAC5 were poorly expressed and SHMT2 was expressed at high levels in GBM U251 cells. NFYB overexpression or SHMT2 knockdown decreased glucose uptake, lactate production, proliferation, migration, and invasion and increased apoptosis and TMZ sensitivity of the cells. NFYB activated HDAC5 to inhibit SHMT2 expression. SHMT2 overexpression nullified the inhibitory effects of NFYB overexpression on glycolysis and TMZ resistance. Thus, NFYB may reduce tumorigenicity and TMZ resistance of GBM through effects on the HDAC5/SHMT2 axis.© The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.