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新型长链非编码 RNA-ZNF281 调控神经胶质瘤干细胞样 U251s 细胞的生长、干性和侵袭。

Novel lncRNA-ZNF281 regulates cell growth, stemness and invasion of glioma stem-like U251s cells.

机构信息

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.

Department of Neurosurgery, General Hospital of Xuzhou Mining Group, the Second Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, China.

出版信息

Neoplasma. 2019 Jan 15;66(1):118-127. doi: 10.4149/neo_2018_180613N391. Epub 2018 Sep 4.

Abstract

Glioma is the most common sub-type of brain tumor. Due to the presence of stem-like cells, it is characterized by poor prognosis, aggressive ability and high post-surgical recurrence rates. Hence, there is critical need to identify molecular mechanisms of glioma stem-like cells. We found a novel lncRNA in the ZNF281 gene and named it lncRNA-ZNF281. We detected the expression of lncRNA-ZNF281 in glioma stem-like cells (U251s), the glioma cell line (U251) and also in normal brain tissue. The expression of lncRNA-ZNF281 was lower in glioma stem-like cells (U251s) and this indicates that lncRNA-ZNF281 can regulate the self-renewal capacity of glioma stem-like cells and stem cell marker expression. Most significantly, lncRNA-ZNF281 inhibits the invasion of glioma stem-like cells by regulating the expression of the NF-κB1 signaling pathway. Our data demonstrates that lncRNA-ZNF281 inhibits the self-renewing ability and invasion of GSCs in vitro and in vivo and can reduce tumorigenicity in the glioma stem-like cell (U251s). The underlying mechanisms may involve the regulation of stem cell markers (CD133, Nestin, OCT4 and Nanog) to reduce the self-renewal ability and regulate the NF-κB1 signaling pathway and inhibit U251s glioma stem-like cell invasion. These finding suggest that lncRNA-ZNF281 could be a successful new therapeutic target in glioma.

摘要

神经胶质瘤是最常见的脑肿瘤亚型。由于存在干细胞样细胞,它的特点是预后不良、侵袭能力强和术后复发率高。因此,迫切需要确定神经胶质瘤干细胞样细胞的分子机制。我们在 ZNF281 基因中发现了一种新的 lncRNA,并将其命名为 lncRNA-ZNF281。我们检测了 lncRNA-ZNF281 在神经胶质瘤干细胞样细胞(U251s)、神经胶质瘤细胞系(U251)和正常脑组织中的表达。lncRNA-ZNF281 在神经胶质瘤干细胞样细胞(U251s)中的表达较低,这表明 lncRNA-ZNF281 可以调节神经胶质瘤干细胞样细胞的自我更新能力和干细胞标记物的表达。最重要的是,lncRNA-ZNF281 通过调节 NF-κB1 信号通路来抑制神经胶质瘤干细胞样细胞的侵袭。我们的数据表明,lncRNA-ZNF281 在体外和体内抑制 GSCs 的自我更新能力和侵袭能力,并降低神经胶质瘤干细胞样细胞(U251s)的致瘤性。潜在的机制可能涉及调节干细胞标记物(CD133、Nestin、OCT4 和 Nanog)以降低自我更新能力,并调节 NF-κB1 信号通路,抑制 U251s 神经胶质瘤干细胞样细胞的侵袭。这些发现表明,lncRNA-ZNF281 可能成为神经胶质瘤的一个成功的新治疗靶点。

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