Glioblastoma is an aggressive type of brain cancer with an extremely poor prognosis. Additionally, the F-box WD repeat-containing protein 7 (FBXW7) is a component of the ubiquitin-proteasome system that has been widely implicated in human cancers. In this study, we investigated the role and mechanism of FBXW7 in glioblastoma. FBXW7 expression was analyzed in normal and glioblastoma tissue samples using The Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) database. Then, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to examine mRNA expression, whereas, western blot analysis was conducted to determine protein levels of the samples. Furthermore, cell apoptosis was assessed using the Annexin V staining method, followed by flow cytometry analysis. Immunoprecipitation (IP) assay was conducted as well to test protein–protein interactions. Lastly, protein expression in tissues was examined by conducting immunohistochemistry (IHC). Results showed that the glioblastoma tissue samples displayed an FBXW7 downregulation compared with normal tissues. In vitro, the overexpression of FBXW7 in glioblastoma cells induced apoptosis, whereas, its knockdown displayed the opposite effect. Mechanistically, FBXW7 interacted with HDAC7 to promote HDAC7 ubiquitination, however, the overexpression of HDAC7 in glioblastoma cells blocked FBXW7-induced apoptosis. Finally, FBXW7 and HDAC7 displayed an inverse correlation in glioblastoma tissues in vivo. Therefore, our data demonstrated an important function of FBXW7 in promoting glioblastoma apoptosis by interacting with HDAC7 and promoting HDAC7 ubiquitination.

中文翻译：

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FBXW7通过调节HDAC7诱导胶质母细胞瘤细胞凋亡

胶质母细胞瘤是一种侵袭性脑癌，预后极差。此外，含有 F-box WD 重复序列的蛋白 7 (FBXW7) 是泛素-蛋白酶体系统的一个组成部分，广泛涉及人类癌症。在这项研究中，我们研究了 FBXW7 在胶质母细胞瘤中的作用和机制。使用癌症基因组图谱多形性胶质母细胞瘤 (TCGA-GBM) 数据库在正常和胶质母细胞瘤组织样本中分析 FBXW7 表达。然后，使用定量逆转录-聚合酶链反应 (RT-PCR) 检查 mRNA 表达，而进行蛋白质印迹分析以确定样品的蛋白质水平。此外，使用膜联蛋白 V 染色法评估细胞凋亡，然后进行流式细胞术分析。还进行了免疫沉淀（IP）测定以测试蛋白质 - 蛋白质相互作用。最后，通过进行免疫组织化学 (IHC) 检查组织中的蛋白质表达。结果表明，与正常组织相比，胶质母细胞瘤组织样本显示出 FBXW7 下调。在体外，FBXW7 在胶质母细胞瘤细胞中的过表达诱导细胞凋亡，而其敲低则表现出相反的效果。从机制上讲，FBXW7 与 HDAC7 相互作用以促进 HDAC7 泛素化，然而，胶质母细胞瘤细胞中 HDAC7 的过表达阻断了 FBXW7 诱导的细胞凋亡。最后，FBXW7 和 HDAC7 在体内胶质母细胞瘤组织中显示出负相关。因此，我们的数据证明了 FBXW7 通过与 HDAC7 相互作用并促进 HDAC7 泛素化在促进胶质母细胞瘤细胞凋亡中的重要功能。