BACKGROUND Circular RNA nuclear factor I X (circNFIX) has been reported to play an important role in glioma progression. However, the mechanism by which circNFIX participates in glioma progression remains poorly understood. METHODS GERIA online were used to analyze the abnormally expressed genes in glioma tissues. The expression levels of circNFIX, microRNA (miR)-378e and Ribophorin-II (RPN2) were measured by quantitative real-time polymerase chain reaction or western blot. Cell cycle distribution, apoptosis, glycolysis, migration and invasion were determined by flow cytometry, special kit and trans-well assays, respectively. The target association between miR-378e and circNFIX or RPN2 was confirmed by luciferase reporter assay, RNA immunoprecipitation and pull-down. Xenograft model was established to investigate the role of circNFIX in vivo. RESULTS The expression of circNFIX was enhanced in glioma tissues and cells compared with matched controls and high expression of circNFIX indicated poor outcomes of patients. Knockdown of circNFIX led to arrest of cell cycle, inhibition of glycolysis, migration and invasion and promotion of apoptosis in glioma cells. circNFIX was a sponge of miR-378e. miR-378e overexpression suppressed cell cycle process, glycolysis, migration and invasion but promoted apoptosis. miR-378e silence abated the suppressive role of circNFIX knockdown in glioma progression. RPN2 as a target of miR-378e was positively regulated via circNFIX by competitively sponging miR-378e. Silencing circNFIX decreased glioma xenograft tumor growth by regulating miR-378e/RPN2 axis. CONCLUSION Knockdown of circNFIX inhibits progression of glioma in vitro and in vivo by increasing miR-378e and decreasing RPN2, providing a novel mechanism for understanding the pathogenesis of glioma.

中文翻译：

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CircNFIX通过调节miR-378e / RPN2轴促进神经胶质瘤的进展。

背景技术已经报道了环状RNA核因子IX（circNFIX）在神经胶质瘤进展中起重要作用。但是，circNFIX参与神经胶质瘤进展的机制仍知之甚少。方法在线使用GERIA分析神经胶质瘤组织中异常表达的基因。通过定量实时聚合酶链反应或western blot检测circNFIX，microRNA（miR）-378e和核糖蛋白-II（RPN2）的表达水平。细胞周期分布，凋亡，糖酵解，迁移和侵袭分别通过流式细胞术，专用试剂盒和trans-well测定法测定。miR-378e与circNFIX或RPN2之间的靶标关联已通过荧光素酶报告基因分析，RNA免疫沉淀和下拉实验得以确认。建立异种移植模型以研究circNFIX在体内的作用。结果与匹配的对照组相比，神经胶质瘤组织和细胞中circNFIX的表达增强，circNFIX的高表达表明患者的预后较差。敲除circNFIX可导致细胞周期停滞，糖酵解抑制，迁移和侵袭以及胶质瘤细胞凋亡的促进。circNFIX是miR-378e的海绵。miR-378e过表达抑制细胞周期过程，糖酵解，迁移和侵袭，但促进细胞凋亡。miR-378e沉默减轻了circNFIX敲低对神经胶质瘤进展的抑制作用。RPN2作为miR-378e的靶标通过circNFIX竞争性地刺激了miR-378e的表达而受到积极调节。沉默circNFIX可通过调节miR-378e / RPN2轴来减少胶质瘤异种移植肿瘤的生长。