Department of Neurosurgery, First Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, Henan, PR China.
Department of Neurosurgery, First Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, Henan, PR China.
Life Sci. 2021 Jul 1;276:119412. doi: 10.1016/j.lfs.2021.119412. Epub 2021 Mar 24.
The effects of PFKFB4 on glycolysis during the cancer progression has been investigated, while its role in glioma remains unclear. The present study evaluated the molecular mechanism of PFKFB4 in glycolysis of glioma progression.
The pan-cancer platform SangerBox was inquired to investigate the E2F2 expression in tumors. The E2F2 expression was studied by qRT-PCR and immunohistochemistry in collected glioma and normal brain tissues and by qRT-PCR and western blot in glioma cells. The relationship between the E2F2 expression in glioma tissues and patients' prognosis was analyzed. The cell malignant phenotype, glycolysis, growth and metastasis were examined by CCK-8, EdU, colony formation, flow cytometry, wound healing, Transwell assays, ELISA kits, and tumorigenesis and metastasis assays. Downstream targets of E2F2 were searched in hTFtarget, followed by pathway enrichment analysis. The expression of these targets and their correlation with E2F2 expression in gliomas were investigated through the GEPIA website. After ChIP and luciferase assays, the effect of the target on glioma was investigated.
E2F2 was overexpressed in glioma patients and predicted poor prognoses. E2F2 promoted cell proliferation, colony formation, DNA synthesis, migration, invasion and glycolysis, and inhibited apoptosis. Meanwhile, inhibition of E2F2 suppressed the growth and metastasis of gliomas. E2F2 elevated the PFKFB4 expression transcriptionally by binding to its promoter and activated PI3K/AKT pathway. The promotion of glioma metastasis and glycolysis by E2F2 was mitigated by PFKFB4 knockdown.
E2F2-mediated transcriptional enhancement of PFKFB4 expression regulated the phosphorylation of PI3K/AKT to promote glioma malignancy progression.
已经研究了 PFKFB4 在癌症进展过程中对糖酵解的影响，但其在神经胶质瘤中的作用尚不清楚。本研究评估了 PFKFB4 在神经胶质瘤进展中糖酵解中的分子机制。
通过 SangerBox 泛癌平台查询肿瘤中 E2F2 的表达情况。通过 qRT-PCR 和免疫组化分析收集的神经胶质瘤和正常脑组织中 E2F2 的表达情况，通过 qRT-PCR 和 Western blot 分析神经胶质瘤细胞中 E2F2 的表达情况。分析神经胶质瘤组织中 E2F2 的表达与患者预后的关系。通过 CCK-8、EdU、集落形成、流式细胞术、划痕愈合、Transwell 测定、ELISA 试剂盒和肿瘤发生和转移测定，检测细胞恶性表型、糖酵解、生长和转移。在 hTFtarget 中搜索 E2F2 的下游靶标，然后进行通路富集分析。通过 GEPIA 网站调查这些靶标在神经胶质瘤中的表达及其与 E2F2 表达的相关性。通过 ChIP 和荧光素酶测定，研究了该靶标对神经胶质瘤的影响。
E2F2 在神经胶质瘤患者中过度表达，并预测预后不良。E2F2 促进细胞增殖、集落形成、DNA 合成、迁移、侵袭和糖酵解，抑制细胞凋亡。同时，抑制 E2F2 可抑制神经胶质瘤的生长和转移。E2F2 通过与启动子结合，转录上调 PFKFB4 的表达，激活 PI3K/AKT 通路。PFKFB4 敲低减轻了 E2F2 对神经胶质瘤转移和糖酵解的促进作用。
E2F2 介导的 PFKFB4 表达转录增强调节了 PI3K/AKT 的磷酸化，从而促进了神经胶质瘤恶性进展。
