Zhu Chengbin, Mao Xinhui, Zhao Hui
Department of Radiotherapy 1, Xinjiang Uygur Autonomous Region People's Hospital, Urumchi, Xinjiang, China.
Medicine (Baltimore). 2020 Feb;99(8):e19171. doi: 10.1097/MD.0000000000019171.
Circular RNAs (circRNAs), a widespread type of noncoding RNA, are produced by reverse splicing with a circular loop structure. Circ_VCAN (hsa_circ_0073237) acts as a novel circRNA, although its roles in the progression and radioresistance of glioma remain unknown.Expressions of circ_VCAN and microRNA-1183 (miR-1183) were analyzed by quantitative real-time PCR, and the functions of circ_VCAN and irradiate in glioma cell proliferation, apoptosis, migration, and invasion were assessed using cell counting kit-8, flow cytometry, Wound healing, and Transwell assays. The interaction between circ_VCAN and miR-1183 was validated dual-luciferase reporter assay.Our results revealed that circ_VCAN was significantly upregulated in radioresistant glioma tissues compared with radiosensitive tissues, and that circ_VCAN expression was negatively correlated with miR-1183 expression in glioma tissues. We also determined that circ_VCAN expression was decreased and miR-1183 expression was increased in U87 and U251 cells after irradiation. Both knockdown of circ_VCAN and treatment with miR-1183 mimics inhibited proliferation, migration, and invasion, and accelerated apoptosis of the irradiated U87 and U251 cells. In addition, luciferase reporter assays revealed that circ_VCAN might function as a sponge for miR-1183. Finally, overexpression of circ_VCAN expedited carcinogenesis and reduced glioma radiosensitivity by regulating miR-1183.Circ_VCAN serves as a potential oncogene of glioma by regulating miR-1183, and plays an essential role in the radioresistance of glioma.
环状RNA（circRNAs）是一种广泛存在的非编码RNA，通过反向剪接产生具有环状结构的RNA。Circ_VCAN（hsa_circ_0073237）作为一种新型环状RNA，其在胶质瘤进展和放射抗性中的作用尚不清楚。通过定量实时PCR分析Circ_VCAN和微小RNA-1183（miR-1183）的表达，并使用细胞计数试剂盒-8、流式细胞术、伤口愈合和Transwell实验评估Circ_VCAN和照射对胶质瘤细胞增殖、凋亡、迁移和侵袭的影响。通过双荧光素酶报告基因实验验证Circ_VCAN与miR-1183之间的相互作用。我们的结果显示，与放射敏感组织相比，Circ_VCAN在放射抗性胶质瘤组织中显著上调，并且Circ_VCAN表达与胶质瘤组织中的miR-1183表达呈负相关。我们还确定，照射后U87和U251细胞中Circ_VCAN表达降低，miR-1183表达增加。Circ_VCAN的敲低和miR-1183模拟物处理均抑制了照射后U87和U251细胞的增殖、迁移和侵袭，并加速了其凋亡。此外，荧光素酶报告基因实验显示，Circ_VCAN可能作为miR-1183的海绵发挥作用。最后，Circ_VCAN的过表达通过调节miR-1183加速了肿瘤发生并降低了胶质瘤的放射敏感性。Circ_VCAN通过调节miR-1183作为胶质瘤的潜在癌基因，并在胶质瘤的放射抗性中起重要作用。
