Abstract
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 polymerase chain reaction. 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.
Highlights
Glioblastoma (GBM) is the most malignant type of glioma with rapid and diffuse infiltrative growth [1, 2]
Our data confirmed that circFOXM1 could serve as a sponge of miR-577 to enhance the progression of GBM by targeting E2F transcription factor 5 (E2F5), which revealed that circFOXM1 might be a biomarker for GBM treatment
By detecting the expression of circFOXM1, we found that circFOXM1 was markedly highly expressed in GBM tumor tissues compared to adjacent normal tissues (Fig. 1C), and it was obviously overexpressed in four GBM cell lines (U251, LN229, T98 and A172) compared with that in NHA cells, especially in LN229 and A172 cells (Fig. 1D)
Summary
Glioblastoma (GBM) is the most malignant type of glioma with rapid and diffuse infiltrative growth [1, 2]. Despite great efforts in treatment, the prognosis of GBM patients is still poor with a typical survival of only about 15 months [3, 4]. GBM often causes a variety of neurological symptoms, which greatly reduces the life quality of patients [5, 6]. It is necessary to better understand the molecular pathogenesis of GBM and develop effective targeted therapies for GBM. Glutaminolysis is an important process to maintain energy metabolism and homeostasis of cancer cells, and it has been found to be closely related to the proliferation of GBM [7, 8]. Elucidating the molecular mechanisms affecting GBM proliferation, metastasis and glutaminolysis is expected to provide effective targets for GBM therapy
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