Circular RNA (circRNA) is a key regulator of tumor progression. However, the role of circFOXM1 in glioblastoma (GBM) progression is unclear. The aim of this study was to investigate the role of circFOXM1 in GBM progression. The expression levels of circFOXM1, miR-577 and E2F transcription factor 5 (E2F5) were examined by real-time quantitative PCR. Cell counting kit 8 assay, EdU staining and transwell assay were used to detect cell proliferation, migration, and invasion. The levels of glutamine, glutamate and α-ketoglutarate were determined to evaluate the glutaminolysis ability of cells. Protein expression was tested by western blot analysis. Dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation assay were employed to verify the interaction between miR-577 and circFOXM1 or E2F5. Mice xenograft model for GBM was constructed to perform in vivo experiments. Our results showed that circFOXM1 was highly expressed in GBM tumor tissues and cells. Silencing of circFOXM1 inhibited GBM cell proliferation, migration, invasion, glutaminolysis, as well as tumor growth. MiR-577 could be sponged by circFOXM1, and its inhibitor could reverse the suppressive effect of circFOXM1 downregulation on GBM progression. E2F5 was a target of miR-577, and the effect of its knockdown on GBM progression was consistent with that of circFOXM1 silencing. CircFOXM1 positively regulated E2F5 expression, while miR-577 negatively regulated E2F5 expression. In conclusion, our data confirmed that circFOXM1 could serve as a sponge of miR-577 to enhance the progression of GBM by targeting E2F5, which revealed that circFOXM1 might be a biomarker for GBM treatment.

中文翻译：

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CircFOXM1 通过调节 miR-577/E2F5 轴促进胶质母细胞瘤的增殖、迁移、侵袭和谷氨酰胺分解。

环状 RNA (circRNA) 是肿瘤进展的关键调节因子。然而，circFOXM1 在胶质母细胞瘤 (GBM) 进展中的作用尚不清楚。本研究的目的是调查 circFOXM1 在 GBM 进展中的作用。通过实时定量 PCR 检测 circFOXM1、miR-577 和 E2F 转录因子 5 (E2F5) 的表达水平。采用细胞计数试剂盒8法、EdU染色法和transwell法检测细胞增殖、迁移和侵袭。测定谷氨酰胺、谷氨酸和α-酮戊二酸的水平以评估细胞的谷氨酰胺分解能力。通过蛋白质印迹分析测试蛋白质表达。采用双荧光素酶报告基因测定、RNA pull-down 测定和 RNA 免疫沉淀测定来验证 miR-577 与 circFOXM1 或 E2F5 之间的相互作用。构建用于 GBM 的小鼠异种移植模型以进行体内实验。我们的结果表明circFOXM1在GBM肿瘤组织和细胞中高表达。circFOXM1 的沉默抑制 GBM 细胞增殖、迁移、侵袭、谷氨酰胺分解以及肿瘤生长。MiR-577 可以被 circFOXM1 吸收，其抑制剂可以逆转 circFOXM1 下调对 GBM 进展的抑制作用。E2F5 是 miR-577 的靶标，其敲低对 GBM 进展的影响与 circFOXM1 沉默的影响一致。CircFOXM1 正向调节 E2F5 表达，而 miR-577 负向调节 E2F5 表达。总之，我们的数据证实 circFOXM1 可以作为 miR-577 的海绵，通过靶向 E2F5 来增强 GBM 的进展，