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

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.

CircSETBP1 Acts as a MiR-149-5p Sponge to Promote Intramuscular Fat Deposition by Regulating CRTCs

“…34 Potential treatment options for glioblastoma may include inhibiting the signal transduction that circFGFR1 induces in the hsa-miR-224-5p/CXCR4 pathway. 35 At present, the circRNA-miRNA-mRNA ceRNA regulatory network is a crucial regulatory mechanism in many biological processes, including the development of disease, cell differentiation, growth, and development. Circ 0123996, for instance, affects the process of diabetic nephropathy by adsorbing miR-149-5p and controlling Bach1.…”

“…Circ 0000064, meantime, can contribute to the development of gastric cancer through controlling miR-621/SYF2 . Potential treatment options for glioblastoma may include inhibiting the signal transduction that circFGFR1 induces in the hsa-miR-224-5p/CXCR4 pathway …”

Underlying mechanisms and clinical potential of circRNAs in glioblastoma

“…Fibroblast growth factor receptor 1 (FGFR1) can promote cancer progression [ 63 , 64 ]. CircFGFR1 is derived from the FGFR1 gene [ 65 ]. CircFGFR1 was shown to enhance GBM tumorigenesis in vivo and in vitro .…”

“…Cell surface chemokine receptor (CXCR4) regulates tumor development [ 66 , 67 ]. The CXCR4 level was positively associated with the circFGFR1 level [ 65 ]. CXCR4 knockout eliminated the promoting effect of circFGFR1 on GBM.…”

“…CXCR4 knockout eliminated the promoting effect of circFGFR1 on GBM. More experiments demonstrated that hsa-miR-224-5p could interact with both circFGFR1 and CXCR4, suggesting that circFGFR1 might sponge hsa-miR-224-5p to elevate the CXCR4 level [ 65 ]. Taken together, these findings indicate that circFGFR1 exerts an oncogenic effect on GBM by enhancing CXCR4 activity through sponging hsa-miR-224-5p [ 65 ].…”