Background: In this study, we determine the potential roles and uncover the regulatory mechanisms of circCCDC66 in regulating cell growth and cell metastasis of glioma.

Methods: qRT-PCR was used to detect the expressions of circCCDC66 in gliomas and tissues. The biological function of circCCDC66 in glioma cell lines was elucidated by functional experiments. Cell counting kit-8 and transwell were used to detect the effect of circCCDC66 on the proliferation, migration and invasion of glioma cells. Bioinformatics analysis was applied to reveal the targets of circCCDC66.

Results: The results showed circCCDC66 was overexpressed in glioma and acted as an oncogene. CircCCDC66 knockdown suppressed the proliferation, migration, and invasion of glioma cells. We constructed a circCCDC66 regulating miRNA network and revealed miR-320a was a potential target of circCCDC66, which was down-regulated in high-grade gliomas compared to low-grade gliomas. Bioinformatics analysis showed circCCDC66-miR-320a/b axis was involved in regulating multiple cancer-related pathways. Furthermore, we identified FOXM1 as a key target of circCCDC66, which was involved in regulating DNA damage response pathways. In mechanism study, circCCDC66 could sponge miR-320a, thereby increasing the expression of FOXM1.

Conclusions: CircCCDC66 could facilitate glioma cells proliferation, invasion and migration by down-regulating miR-320a and up-regulating FOXM1.