Abstract The dysregulated lncRNA play essential roles in glioma development. This study aimed to investigate the role and mechanism of lncRNA potassium voltage-gated channel subfamily Q member 1 opposite strand/ antisense transcript 1 (KCNQ1OT1) in glioma progression. Tumor tissues and adjacent normal samples were collected from 30 glioma patients. The expression levels of lncRNA KCNQ1OT1, microRNA (miR)-338-3p and ribonucleotide reductase M2 (RRM2) were detected by quantitative real-time polymerase chain reaction or western blot analyses. Levels of cell viability, apoptosis, cell migration and invasion in glioma cell lines were determined using cell counting kit-8, flow cytometry with annexin V-FITC and trans-well assays, respectively. The role of KCNQ1OT1 in glioma development in vivo was investigated using a xenograft model. The target association between miR-338-3p and KCNQ1OT1 or RRM2 was validated by luciferase reporter assay. The results found that expression of KCNQ1OT1 was enhanced in glioma tissues and cells, and KCNQ1OT1 knockdown inhibited cell viability, migration and invasion, and xenograft tumor growth, but promoted apoptosis. miR-338-3p was targeted via KCNQ1OT1 and could reverse the effect of KCNQ1OT1 on glioma progression. RRM2 was targeted via miR-338-3p and attenuated the suppressive effect of miR-338-3p on glioma cell viability, migration and invasion. Besides, KCNQ1OT1 overexpression increased RRM2 expression, and this event was weakened via miR-338-3p up-regulation. In conclusion, the present finding suggest that silencing of KCNQ1OT1 can suppress the development and progression of glioma by up-regulating miR-338-3p and down-regulating RRM2.

中文翻译：

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敲低 lncRNA KCNQ1OT1 通过调节 miR-338-3p/RRM2 抑制胶质瘤进展

摘要 失调的 lncRNA 在胶质瘤的发生发展中发挥着重要作用。本研究旨在探讨lncRNA钾电压门控通道亚家族Q成员1相反链/反义转录物1（KCNQ1OT1）在胶质瘤进展中的作用和机制。从 30 名神经胶质瘤患者收集肿瘤组织和邻近的正常样本。通过定量实时聚合酶链反应或蛋白质印迹分析检测 lncRNA KCNQ1OT1、微小 RNA (miR)-338-3p 和核糖核苷酸还原酶 M2 (RRM2) 的表达水平。分别使用细胞计数试剂盒 8、具有膜联蛋白 V-FITC 的流式细胞术和 trans-well 测定法测定神经胶质瘤细胞系中细胞活力、凋亡、细胞迁移和侵袭的水平。使用异种移植模型研究了 KCNQ1OT1 在 体内 胶质瘤发展中的作用。miR-338-3p 和 KCNQ1OT1 或 RRM2 之间的靶标关联通过荧光素酶报告基因测定进行验证。结果发现，KCNQ1OT1在胶质瘤组织和细胞中的表达增强，KCNQ1OT1敲低抑制了细胞活力、迁移和侵袭以及异种移植肿瘤的生长，但促进了细胞凋亡。miR-338-3p 通过 KCNQ1OT1 靶向，可以逆转 KCNQ1OT1 对胶质瘤进展的影响。RRM2 通过 miR-338-3p 靶向并减弱 miR-338-3p 对神经胶质瘤细胞活力、迁移和侵袭的抑制作用。此外，KCNQ1OT1 过表达增加了 RRM2 的表达，并且通过 miR-338-3p 上调减弱了这一事件。总之，目前的发现表明，KCNQ1OT1 的沉默可以通过上调 miR-338-3p 和下调 RRM2 来抑制神经胶质瘤的发展和进展。