Abstract
Circular RNAs contribute to the progression of glioma. However, the biological role and underlying mechanism of circ_0082375 in glioma remain unclear. Quantitative real-time PCR and Western blot assay were used to evaluate the expression levels of circ_0082375, microRNA-485-5p, and Wnt family member 7B (Wnt7B). The overall survival of glioma patients was estimated by the Kaplan–Meier curve. Cell proliferation, apoptosis, invasion, and migration were detected by cell counting kit-8, 5-ethynyl-2 -deoxyuridine (EdU) staining, flow cytometry, and transwell assays, respectively. Glucose level and lactate production were determined using glucose and lactate assay kits. In vitro angiogenesis assay was used to evaluate the angiogenesis of glioma cells. The interaction between microRNA (miR)-485-5p and circ_0082375 or Wnt family member 7B (Wnt7B) was verified by dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft model was used to verify the function of circ_0082375 in vivo. circ_0082375 was upregulated in glioma tissues, and it was closely related to the prognosis of glioma patients. circ_0082375 knockdown suppressed cell proliferation, migration, invasion, angiogenesis, glycolysis, and epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in glioma cells. irc_0082375 was a sponge of miR-485-5p, which directly targeted Wnt7B. Knockdown of circ_0082375 inhibited the malignancy, angiogenesis, and glycolysis of glioma cells in vitro by sponging miR-485-5p. Besides, circ_0082375 knockdown hampered the growth of glioma growth by regulating the miR-485-5p/Wnt7B axis in vivo. Altogether, circ_0082375 regulated miR-485-5p/Wnt7B axis to promote the malignancy, angiogenesis, and glycolysis of glioma cells, thereby contributing to the progression of glioma.
Highlights
Glioma is a common primary intracranial tumor with strong invasiveness [1]
Mounting evidence suggests that circRNAs are partly responsible for the tumorigenesis and progression of glioma. circ_0082375, derived from the CPA4 gene, was first identified to be significantly increased in glioma by high-throughput circRNA microarray assay
Unlike normal cells that rely on mitochondrial oxidation to produce energy, tumor cells mainly generate metabolic energy by glycolysis [22]
Summary
Glioma is a common primary intracranial tumor with strong invasiveness [1]. It was reported that the morbidity of glioma has risen from 5.9 per 100,000 people in 1973 to 6.61 per 100,000 people in 2016 [2]. Seeking a novel biomarker for the treatment of glioma patients is urgently required. CircRNAs partake in the regulation of multiple pathological processes in glioma, containing EMT, proliferation, apoptosis, migration, invasion, angiogenesis, and glycolysis [5,6]. CircRNA pleiotrophin facilitates glioma cell proliferation and stemness by interacting with miR-145-5p and miR-330-5p [7]. CircPITX1 reduces radiation sensitivity of glioma cells by elevating glycolysis through regulating the miR-329-3p/NIMA2 axis [8]. CircPITX1 reduces radiation sensitivity of glioma cells by elevating glycolysis through regulating the miR-329-3p/NIMA2 axis [8]. hsa_circ_0082375 (chr7: 129950626–129964020), derived from the carboxypeptidaseA4 (CPA4) gene, has been uncovered to be upregulated in glioma tissues of 73 patients [9], whereas the underlying mechanism of hsa_circ_0082375 in glioma has not been clearly explained yet
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