<scp>circTOP2A</scp> functions as a <scp>ceRNA</scp> to promote glioma progression by upregulating <scp>RPN2</scp>

Competing endogenous RNA (ceRNA) mediated signaling pathway dysregulation provides great insights into comprehensively understanding the molecular mechanism and combined targeted therapy for glioblastoma. circRNA is characterized by high stability, tissue/developmental stage-specific expression and abundance in brain and plays significant roles in initiation and progression of cancer. Our previous published data have demonstrated that RPN2 was significantly upregulated in glioma and promoted the tumor progression via the activation of Wnt/β-catenin pathway, furthermore, we proved that miR-422a regulated the Wnt/β-catenin signaling pathway by directly targeting RPN2. In this study, based on the glioblastoma microarray profiles, we identified the upstream circTOP2A, which completely bound to the miR-422a and co-expressed with the RPN2. circTOP2A was significantly overexpressed in glioma and conferred to poor prognosis. circTOP2A could regulate RPN2 expression by sponging miR-422a, verified by Western blot, dual-luciferase reporter gene assay and RNA pull down. Functional assays including CCK8, Transwell and FITC Annexin V were performed to explore RPN2 mediated role of circTOP2A effect on the glioma malignant phenotype. Additionally, TOP/FOP and Immunofluorescence analysis were used to confirm that sh-circTOP2A could suppress the Wnt/β-catenin pathway partly through RPN2. Finally, Tumor xenograft model was applied to validate the biological function of circTOP2A in vivo. Taken together, our findings reveal the critical role of circTOP2A in promoting glioma proliferation and invasion via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for glioma patients.