Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, 215004, Suzhou, China.
Rugao Hospital Affiliated to Nantong University, 226500, Nantong, Jiangsu, China.
Cell Death Dis. 2021 May 25;12(6):536. doi: 10.1038/s41419-021-03834-1.
Many studies have reported that circular RNAs play a vital role in the malignant progression of human cancers. However, the role and underlying mechanism of circRNAs in the development of gliomas have not been fully clarified. In this study, we found that circ_0001367 was downregulated in glioma tissues and showed a close correlation with glioma patient survival. Functional assays demonstrated that upregulation of circ_0001367 could suppress the proliferation, migration and invasion of glioma cells in vitro and inhibit glioma growth in vivo. Furthermore, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay indicated that circ_0001367 can serve as a sponge for miR-431 and that miR-431 acts as an oncogene by regulating neurexin 3 (NRXN3). In addition, rescue experiments verified that circ_0001367 could regulate both the expression and function of NRXN3 in a miR-431-dependent manner. In conclusion, circ_0001367 functions as an suppressor in glioma by targeting the miR-431/NRXN3 axis and may be a promising therapeutic target against gliomas.
许多研究表明,环状 RNA 在人类癌症的恶性进展中发挥着重要作用。然而,环状 RNA 在胶质瘤发展中的作用及其潜在机制尚未完全阐明。在这项研究中,我们发现 circ_0001367 在胶质瘤组织中下调,并与胶质瘤患者的生存密切相关。功能分析表明,circ_0001367 的上调可以抑制胶质瘤细胞在体外的增殖、迁移和侵袭,并抑制体内胶质瘤的生长。此外,生物信息学分析、荧光素酶报告基因检测和 RNA 免疫沉淀实验表明,circ_0001367 可以作为 miR-431 的海绵,而 miR-431 通过调节神经连接蛋白 3(NRXN3)发挥致癌作用。此外,挽救实验验证了 circ_0001367 可以通过 miR-431 依赖性方式调节 NRXN3 的表达和功能。总之,circ_0001367 通过靶向 miR-431/NRXN3 轴在胶质瘤中发挥抑制作用,可能成为治疗胶质瘤的有前途的靶点。