Gong Wei, Zheng Jian, Liu Xiaobai, Liu Yunhui, Guo Junqing, Gao Yana, Tao Wei, Chen Jiajia, Li Zhiqing, Ma Jun, Xue Yixue
Department of Neurobiology, College of Basic Medicine, China Medical UniversityShenyang, China; Key Laboratory of Cell Biology, Ministry of Public Health of China, Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical UniversityShenyang, China.
Department of Neurosurgery, Shengjing Hospital of China Medical UniversityShenyang, China; Liaoning Research Center for Translational Medicine in Nervous System DiseaseShenyang, China.
Front Cell Neurosci. 2017 Mar 22;11:84. doi: 10.3389/fncel.2017.00084. eCollection 2017.
Accumulating evidence has highlighted the potential role of long non-coding RNAs (lncRNAs) as biomarkers and therapeutic targets in solid tumors. Here, we elucidated the function and possible molecular mechanisms of lncRNA KCNQ1OT1 in human glioma U87 and U251 cells. Quantitative Real-Time polymerase chain reaction (qRT-PCR) demonstrated that KCNQ1OT1 expression was up-regulated in glioma tissues and cells. Knockdown of KCNQ1OT1 exerted tumor-suppressive function in glioma cells. Moreover, a binding region was confirmed between KCNQ1OT1 and miR-370 by dual-luciferase assays. qRT-PCR showed that miR-370 was down-regulated in human glioma tissue and cells. In addition, restoration of miR-370 exerted tumor-suppressive function via inhibiting cell proliferation, migration and invasion, while promoting the apoptosis of human glioma cells. Knockdown of KCNQ1OT1 decreased the expression level of Cyclin E2 (CCNE2) by binding to miR-370. Further, miR-370 bound to CCNE2 3'UTR region and decreased the expression of CCNE2. These results provided a comprehensive analysis of KCNQ1OT1-miR-370-CCNE2 axis in human glioma cells and might provide a novel strategy for glioma treatment.
越来越多的证据表明，长链非编码RNA（lncRNA）在实体瘤中作为生物标志物和治疗靶点具有潜在作用。在此，我们阐明了lncRNA KCNQ1OT1在人胶质瘤U87和U251细胞中的功能及可能的分子机制。定量实时聚合酶链反应（qRT-PCR）表明，KCNQ1OT1在胶质瘤组织和细胞中表达上调。敲低KCNQ1OT1在胶质瘤细胞中发挥肿瘤抑制功能。此外，通过双荧光素酶报告基因检测证实了KCNQ1OT1与miR-370之间存在结合区域。qRT-PCR显示，miR-370在人胶质瘤组织和细胞中表达下调。此外，恢复miR-370通过抑制细胞增殖、迁移和侵袭，同时促进人胶质瘤细胞凋亡发挥肿瘤抑制功能。敲低KCNQ1OT1通过与miR-370结合降低细胞周期蛋白E2（CCNE2）的表达水平。此外，miR-370与CCNE2的3'UTR区域结合并降低CCNE2的表达。这些结果对人胶质瘤细胞中的KCNQ1OT1-miR-370-CCNE2轴进行了全面分析，可能为胶质瘤治疗提供新策略。
