Circular RNA carboxypeptidase A4 (circCPA4) has been shown to involve in the tumorigenesis of glioma. However, the function and the molecular mechanism of circCPA4 in glioma remain inadequate. Levels of circCPA4 and microRNA (miR)-760 were detected by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were analyzed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, flow cytometry, and transwell assays, respectively. Western blot was used to detect the protein levels of matrix metallopeptidase 2 (MMP2), MMP9 and myocyte enhancer factor 2D (MEF2D). The interaction between miR-760 and circCPA4 or MEF2D was analyzed by the dual-luciferase reporter assay or RNA pull-down assay. In vivo experiments were conducted using murine xenograft models. We found circCPA4 was highly expressed in glioma, and circCPA4 knockdown suppressed tumor cell proliferative, migratory and invasive behaviors, but enhanced cell apoptosis and radiosensitivity in glioma. CircCPA4 directly bound to miR-760 to suppress its expression, and miR-760 inhibition reversed circCPA4 knockdown-mediated inhibition of cell malignant phenotypes in glioma. MEF2D was a target of miR-760, and miR-760 performed anti-tumor effects by targeting MEF2D in glioma cells. Meanwhile, we found circCPA4 could indirectly regulate MEF2D by sponging miR-760. Importantly, xenograft analysis suggested that circCPA4 knockdown impeded tumor growth in vivo via regulating miR-760 and MEF2D. In conclusion, circCPA4 knockdown suppressed cell malignant phenotypes in glioma via miR-760/MEF2D axis to impede the progression of glioma, suggesting potential therapeutic targets for glioma treatment.

环状RNA羧肽酶A4（circCPA4）已被证明参与神经胶质瘤的肿瘤发生。然而，circCPA4在神经胶质瘤中的功能和分子机制仍然不足。通过定量实时聚合酶链反应检测circCPA4和microRNA（miR）-760的水平。使用MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴化物），集落形成，流式细胞术和transwell分析法分别分析了细胞增殖，凋亡，迁移和侵袭。Western印迹用于检测基质金属肽酶2（MMP2），MMP9和肌细胞增强因子2D（MEF2D）的蛋白水平。miR-760与circCPA4或MEF2D之间的相互作用通过双荧光素酶报告基因分析或RNA下拉分析进行了分析。使用鼠异种移植模型进行体内实验。我们发现circCPA4在神经胶质瘤中高表达，而circCPA4敲低抑制了肿瘤细胞的增殖，迁移和侵袭行为，但增强了神经胶质瘤中的细胞凋亡和放射敏感性。CircCPA4直接与miR-760结合以抑制其表达，miR-760的抑制作用逆转了circCPA4敲低介导的胶质瘤细胞恶性表型的抑制作用。MEF2D是miR-760的靶标，miR-760通过靶向神经胶质瘤细胞中的MEF2D来发挥抗肿瘤作用。同时，我们发现circCPA4可以通过刺激miR-760间接调节MEF2D。重要的是，异种移植分析表明，circCPA4敲低通过调节miR-760和MEF2D阻碍了体内肿瘤的生长。总之，circCPA4敲低可通过miR-760 / MEF2D轴抑制神经胶质瘤中的细胞恶性表型，从而阻止神经胶质瘤的发展，