Hsa_circ_0000177-miR-638-FZD7-Wnt Signaling Cascade Contributes to the Malignant Behaviors in Glioma.

Abstract

As a new member of the noncoding RNA family, circular RNAs (circRNAs) have been demonstrated as critical regulators in various physiological and pathological processes, such as tumorigenesis. However, the role of circRNAs has not been well understood until now. In our study, we found that circRNA hsa_circ_0000177 was upregulated in glioma tissues and cell lines. Also, hsa_circ_0000177 overexpression was associated with poor prognosis in glioma patients. Through functional experiments, we found that hsa_circ_0000177 knockdown dramatically inhibited glioma cell proliferation and invasion in vitro. Consistently, hsa_circ_0000177 knockdown significantly repressed glioma growth in vivo. In terms of mechanism, we used bioinformatics analysis and identified hsa_circ_0000177 as a miR-638 sponge. We showed that miR-638 inhibition could restore the proliferation and invasion of glioma cells transfected with hsa_circ_0000177 small interfering RNA. Furthermore, we demonstrated that frizzled class receptor 7 (FZD7) was targeted by miR-638 and upregulated by hsa_circ_0000177. Through upregulating FZD7 expression, hsa_circ_0000177 activated Wnt signaling and facilitated glioma growth. Taken together, our study revealed a novel signaling pathway involved in glioma progression.