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长链非编码 RNA LINC00511 通过靶向 miR-124-3p/CCND2 轴被 SP1 诱导加速了胶质瘤的进展。

Long noncoding RNA LINC00511 induced by SP1 accelerates the glioma progression through targeting miR-124-3p/CCND2 axis.

机构信息

Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, P.R. China.

出版信息

J Cell Mol Med. 2019 Jun;23(6):4386-4394. doi: 10.1111/jcmm.14331. Epub 2019 Apr 11.

Abstract

Mounting evidence suggests the vital roles of long noncoding RNA (lncRNAs) in the glioma. However, the role of LINC00511 in gliomagenesis is still uncovered. Here, in this study, we aim to investigate the effects of LINC00511 on the glioma cancer phenotype and its deepgoing mechanism. Results indicated that LINC00511 was up-regulated in glioma tissues and cell lines, moreover its overexpression positively correlated with the poor prognosis and advanced pathological stages. For the upstream regulation, LINC00511 was epigenetically up-regulated by transcription factor specificity protein 1 (SP1). Gain and loss of functional experiments demonstrated that LINC00511 promoted the proliferation and invasion of glioma cells in vitro. The knockdown of LINC00511 repressed the tumour growth in vivo. Mechanistically, LINC00511 positively regulated the CCND2 expression via competitively sponging with miR-124-3p. Overall, our finding illuminates that LINC00511 is induced by SP1 and accelerates the glioma progression through targeting miR-124-3p/CCND2 axis, constructing the SP1/LINC00511/miR-124-3p/CCND2 axis.

摘要

越来越多的证据表明长链非编码 RNA(lncRNA)在神经胶质瘤中起着至关重要的作用。然而,LINC00511 在神经胶质瘤发生中的作用仍未被揭示。在本研究中,我们旨在研究 LINC00511 对神经胶质瘤表型的影响及其深入的机制。结果表明,LINC00511 在神经胶质瘤组织和细胞系中上调,此外,其过表达与不良预后和高级别病理阶段呈正相关。对于上游调控,LINC00511 被转录因子特异性蛋白 1(SP1)通过表观遗传方式上调。功能增益和缺失实验表明,LINC00511 促进了神经胶质瘤细胞在体外的增殖和侵袭。LINC00511 的敲低抑制了体内肿瘤的生长。在机制上,LINC00511 通过与 miR-124-3p 竞争结合来正向调节 CCND2 的表达。总之,我们的研究结果表明,LINC00511 被 SP1 诱导,并通过靶向 miR-124-3p/CCND2 轴加速神经胶质瘤的进展,构建了 SP1/LINC00511/miR-124-3p/CCND2 轴。

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