Circular RNA circFGFR1 Functions as an Oncogene in Glioblastoma Cells through Sponging to hsa-miR-224-5p.

Qian Zhang,Yong Wang,Zhenyu Zhang,Peng Gao,Shan Chen,Hao Guo,Yingwei Zhen,Sainan Li

doi:10.1155/2022/7990251

Abstract

Recently, increased studies have shown the important regulatory role of circular RNA (circRNA) in cancer progression and development, including glioblastoma (GBM). However, the function of circRNAs in glioblastoma is still largely unclear. Here, we state that circFGFR1 is elevated in glioma cells, resulting in aggravated glioma aggravated malignancy. The upregulation of circFGFR1 also promotes glioma growth in mouse xenograft models. Furthermore, CXCR4 level in glioma cells is positively correlated with circFGFR1 level, and higher CXCR4 expression is found in circFGFR1 overexpression groups. The effect of circFGFR1 on glioma malignancy is abolished in CXCR4 knockout cells. Then, RIP, RNA pull-down, and luciferase reporter assay results showed that hsa-miR-224-5p directly binds to circFGFR1 and CXCR4 mRNA. The CXCR4 3′-untranslated region (UTR) activated luciferase activity was reduced with hsa-miR-224-5p transfection, while it is reversed when cotransfected with circFGFR1, indicating that circFGFR1 acts as a hsa-miR-244-5p sponge to increase CXCR4 expression. The hsa-miR-224-5p expression is negatively corrected with the glioma malignancy through inhibiting CXCR4 level. Besides, the circFGFR1-induced regulation in glioma malignancy is also abrogated in hsa-miR-224-5p knockout cells. Taken together, our findings suggest that circFGFR1 plays a critical role in the tumorigenic behaviors in glioma cells by upregulating CXCR4 expression via sponging to hsa-miR-224-5p. These findings provide a new perspective on circRNAs during GBM development.

Highlights

Glioblastoma (GBM) is one of the most devastating cancers [1]
Despite recent advances in therapy, such as radiotherapy, chemotherapy, and mass surgical resection, the median survival is less than 15 months, and the 2-year survival rate is less than 5% [2, 3]
The membranes were blocked with Tris-buffered saline supplementing with 0.1% Tween 20 (TBST) and 5% fat-free milk for 1 h and incubated with corresponding antibodies at 4°C overnight

Summary

Introduction

Glioblastoma (GBM) is one of the most devastating cancers [1]. Further understanding the potential molecular mechanisms in glioma progression is an emergency for exploring more effective therapeutic strategies. Benefit from the covalently closed-loop structures without 5′ to 3′ polarity and polyadenylated tail [5], circRNAs are much more stable than linear RNAs in the cytoplasm, which might contribute to its significant role in different diseases and pathophysiological processes, including cancer progression [6,7,8]. Zhu et al state that dysregulated circRNAs displayed a correlation with tumorigenesis and the development of GBM through bioinformatics, indicating the important role of circRNAs in glioma [9]. Clarifying the molecular mechanisms induced by circRNAs in glioma may conduce to promising therapeutic candidate development

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