Background
Glioblastoma (GBM) is a highly aggressive cancer having a dismal prognosis. N6-methyladenosine (m6A) is closely related to GBM progression. The significance of m6A modifications depends on the m6A readers, whose functions in glioma progression are largely unknown. This study sought to investigate the expression of the m6A related gene in glioma and its effect on the malignant progression of glioma.
Conclusions
IGF2BP3 expression in glioma is positively correlated with tumor grade and enhanced glioma cell proliferation, invasion, and tumorigenicity. IGF2BP3 knockdown decreased the expression of CDK1 and the cell cycle process. The current study showed that IGF2BP3 may serve as a biomarker of prognosis and a therapeutic target in glioma.
Methods
The expression differences between low-grade gliomas (LGGs) and high-grade gliomas (HGGs), and among 19 m6A-related genes were analyzed by The Cancer Genome Atlas (TCGA). Survival probability was analyzed in terms of the high or low expression of insulin growth factor-2 binding protein 3 (IGF2BP3) in the TCGA data set. The clinicopathological data of 40 patients with glioma were analyzed retrospectively, and the expression of IGF2BP3 in the tumor tissues was analyzed by immunohistochemistry (IHC). Lentiviral vectors harboring short-hairpin RNA (shRNA) were used to knock down IGF2BP3 in the glioma cell lines U87 and U251, and the
Results
The sequencing of TCGA data identified IGF2BP3 as the most significantly altered m6A-related gene. Patients with high IGF2BP3 expression had a significantly reduced survival probability (P<0.001) compared to those with low IGF2BP3 expression. IGF2BP3 was more upregulated in the HGGs than the LGGs. The downregulation of IGF2BP3 inhibited the proliferation, migration, and invasiveness of the glioma cells, and xenograft tumor growth in the mice. According to TCGA data, IGF2BP3 was closely related to cell cycle regulators, such as cyclin-dependent kinase 1 (CDK1) and cell-division cycle protein 20 homologue (CDC20). Further, the knockdown of IGF2BP3 affected the expression of CDK1 and the cell cycle process. Conclusions: IGF2BP3 expression in glioma is positively correlated with tumor grade and enhanced glioma cell proliferation, invasion, and tumorigenicity. IGF2BP3 knockdown decreased the expression of CDK1 and the cell cycle process. The current study showed that IGF2BP3 may serve as a biomarker of prognosis and a therapeutic target in glioma.