Department of Neurosurgery, Suzhou Science and Technology Town Hospital, Suzhou, Jiangsu, China (mainland).
Department of Neurosurgery, Yidu Central Hospital of Weifang, Weifang, Shandong, China (mainland).
Med Sci Monit. 2019 Aug 28;25:6454-6461. doi: 10.12659/MSM.918676.
BACKGROUND Circular RNA circMTO1 has been reported to inhibit the progression of many types of cancers. However, the role of circMTO1 in the progression of glioblastoma remains unclear. The purpose of our study was to explore the potential involvement of circMTO1 in glioblastoma. MATERIAL AND METHODS The expression of circMTO1 in human glioblastoma tissues was determined via quantitative real-time polymerase chain reaction (qRT-PCR). The effect of circMTO1 on proliferation of human glioblastoma cell line U251 was assessed through the Cell Counting Kit-8 (CCK-8) and colony formation assay. The regulatory interaction between circMTO1 and miR-92 was explored by bioinformatics prediction and luciferase reporter assay. RESULTS We showed that circMTO1 was markedly downregulated in glioblastoma tissues compared with adjacent normal tissues. Lower circMTO1 level was significantly associated with shorter overall survival among patients with glioblastoma. In addition, circMTO1 inhibited proliferation of cell U251 cells. Mechanistically, circMTO1 upregulates the expression of WWOX in U251 cells, and WWOX mediates circMTO1-induced inhibition of proliferation of U251 cells. In addition, miR-92 downregulates the expression of WWOX by the targeting its mRNA 3' UTR. More importantly, circMTO1 directly interact with miR-92, and subsequently serves as a miRNA sponge to upregulate WWOX expression. CONCLUSIONS Our results demonstrate that circMTO1 inhibits the proliferation of glioblastoma cells via the miR-92/WWOX signaling pathway.
环状 RNA circMTO1 已被报道能抑制多种类型癌症的进展。然而，circMTO1 在胶质母细胞瘤进展中的作用尚不清楚。我们的研究目的是探讨 circMTO1 在胶质母细胞瘤中的潜在作用。
通过实时定量聚合酶链反应(qRT-PCR)检测人胶质母细胞瘤组织中 circMTO1 的表达。通过细胞计数试剂盒-8(CCK-8)和集落形成实验评估 circMTO1 对人胶质母细胞瘤细胞系 U251 增殖的影响。通过生物信息学预测和荧光素酶报告实验探讨 circMTO1 与 miR-92 之间的调控相互作用。
与邻近正常组织相比，circMTO1 在胶质母细胞瘤组织中明显下调。较低的 circMTO1 水平与胶质母细胞瘤患者的总生存期较短显著相关。此外，circMTO1 抑制细胞 U251 细胞的增殖。机制上，circMTO1 在 U251 细胞中上调 WWOX 的表达，而 WWOX 介导 circMTO1 诱导的 U251 细胞增殖抑制。此外，miR-92 通过靶向其 mRNA 3'UTR 下调 WWOX 的表达。更重要的是，circMTO1 直接与 miR-92 相互作用，并随后作为 miRNA 海绵上调 WWOX 的表达。
我们的结果表明，circMTO1 通过 miR-92/WWOX 信号通路抑制胶质母细胞瘤细胞的增殖。
