Knockdown of Long Non-Coding RNA KCNQ1OT1 Restrained Glioma Cells' Malignancy by Activating miR-370/CCNE2 Axis.
Knockdown of Long Non-Coding RNA KCNQ1OT1 Restrained Glioma Cells' Malignancy by Activating miR-370/CCNE2 Axis.
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DOI：
10.3389/fncel.2017.00084
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发表时间：
2017
影响因子：
5.3
通讯作者：
Xue Y
中科院分区：
文献类型：
--
作者：
Gong W;Zheng J;Liu X;Liu Y;Guo J;Gao Y;Tao W;Chen J;Li Z;Ma J;Xue Y
越来越多的证据强调了长链非编码RNA（lncRNAs）作为实体肿瘤生物标志物和治疗靶点的潜在作用。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。实时定量聚合酶链反应（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作用。此外，通过双荧光素酶实验证实了KCNQ1OT1和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的表达通过抑制细胞增殖、迁移和侵袭，同时促进人胶质瘤细胞凋亡而发挥肿瘤抑制作用。敲低KCNQ1OT1通过与miR - 370结合降低了细胞周期蛋白E2（CCNE2）的表达水平。进一步研究发现，miR - 370与CCNE2的3′非翻译区（3′UTR）结合并降低CCNE2的表达。这些结果全面分析了人胶质瘤细胞中的KCNQ1OT1 - miR - 370 - CCNE2轴，可能为胶质瘤治疗提供一种新的策略。
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.