circTOP2A functions as a ceRNA to promote glioma progression by upregulating RPN2.

Competing endogenous RNA (ceRNA)-mediated signaling pathway dysregulation provides great insight 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 the initiation and progression of cancer. Our previous published data have demonstrated that RPN2 was significantly upregulated in glioma and promoted tumor progression via the activation of the 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 miR-422a and was co-expressed with the RPN2. circTOP2A was significantly overexpressed in glioma and conferred a poor prognosis. circTOP2A could regulate RPN2 expression by sponging miR-422a, verified by western blot, dual-luciferase reporter gene assay, and RNA pull-down assay. Functional assays including CCK8, transwell and FITC-annexin V were performed to explore the RPN2-mediated role of the 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, a 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.

Sun J ，Wang J ，Li M ，Li S ，Li H ，Lu Y ，Li F ，Xin T ，Jin F ... -  《-》

MicroRNA‑422a functions as a tumor suppressor in glioma by regulating the Wnt/β‑catenin signaling pathway via RPN2.

Sun J ，Chen Z ，Xiong J ，Wang Q ，Tang F ，Zhang X ，Mo L ，Wang C ，Fan W ，Wang J ... -  《-》

RPN2 is targeted by miR-181c and mediates glioma progression and temozolomide sensitivity via the wnt/β-catenin signaling pathway.

Sun J ，Ma Q ，Li B ，Wang C ，Mo L ，Zhang X ，Tang F ，Wang Q ，Yan X ，Yao X ，Wu Q ，Shu C ，Xiong J ，Fan W ，Wang J ... -  《Cell Death & Disease》

CircNFIX promotes progression of glioma through regulating miR-378e/RPN2 axis.

Ding C ，Wu Z ，You H ，Ge H ，Zheng S ，Lin Y ，Wu X ，Lin Z ，Kang D ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Sevoflurane represses the progression of glioma by the regulation of circ_0037655/miR-130a-5p/RPN2 axis.

Sevoflurane (SEV) is a common anesthetic to inhibit glioma progression. The previous studies have indicated the molecular mechanisms of SEV function in glioma. The objective of this study was to explore the association of circ_00037655 with SEV in glioma. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. Cell proliferation was analyzed using Edu assay and colony formation assay. Flow cytometry was applied to determine cell apoptosis. Protein analysis was performed via western blot. Cell migration and invasion were assessed by transwell assay. Circ_0037655, microRNA-130a-5p (miR-130a-5p) and ribophorin II (RPN2) levels were detected using the quantitative real-time polymerase chain reaction (qRT-PCR). Dual-luciferase reporter, RNA immunoprecipitation (RIP) and pull-down assays were used to analyze target interaction. The effect of circ_0037655 on SEV in vivo was researched by xenograft models. SEV reduced cell viability, proliferation, migration and invasion but induced apoptosis of glioma cells. Circ_0037655 expression was inhibited after SEV treatment in glioma cells. The effects of SEV on glioma cell behaviors were attenuated by upregulation of circ_0037655. Circ_0037655 interacted with miR-130a-5p and miR-130a-5p targeted RPN2. Circ_0037655 or miR-130a-5p regulated the anti-tumor function of SEV in glioma by targeting miR-130a-5p or RPN2. Circ_0037655 affected the expression of RPN2 via targeting miR-130a-5p. Circ_0037655 relieved SEV-induced glioma growth inhibition in vivo by mediating miR-130a-5p and RPN2 levels. SEV inhibited the malignant progression of glioma cells partly by regulating the circ_0037655/miR-130a-5p/RPN2 axis.

Zhu J ，Xie B ，Huang G ，Li Y ，Liu Z ... -  《-》