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抑制 JMJD6 表达可降低神经胶质瘤干细胞的增殖、迁移和侵袭。

Inhibition of JMJD6 expression reduces the proliferation, migration and invasion of neuroglioma stem cells.

出版信息

Neoplasma. 2017;64(5):700-708. doi: 10.4149/neo_2017_507.

Abstract

Neuroglioma is the most common form of human primary malignant brain tumor, more and more studies recently showed only a small subpopulation of glioma cells which called glioma stem cells have true tumorigenic potential. Meanwhile, it was reported the overexpression of JMJD6 protein is closely involvement with the occurrence and development of multiple tumors, and JMJD6 is required for the differentiation of multiple organ, tissues and cells during embryogenesis. However, the influence of JMJD6 overexpression on neuroglioma development is unclear now. Hence, to explore the effects of JMJD6 expression on neuroglioma, we firstly isolated glioma stem cells by using CD133 MicroBead Kit, and identified via neurosphere-forming assay and Immunofluorescence staining. At the same time, we investigated the effects and mechanism of JMJD6 on the proliferation, migration and invasion of glioma stem cells through MTT, transwell assays and the Cignal finder cancer 10-pathway reporter array. The results demonstrated that the glioma neurosphere cells positively expressed stem cell marker SOX2, neuroectodermal stem cell marker Nestin, and also expressed astrocytes marker GFAP and neurons marker β-tubulin III fter FBS-induced differentiation for a week, which proved the glioma neurosphere cells have the self-renewal and multipotential differentiation capacity. Moreover, shRNA lentiviral vector mediated knockdown of JMJD6 in glioma stem cells led to decreased proliferation, migration and invasion, the underlying molecular mechanism is related to the weaken of Wnt signaling pathway and strengthen of p53 signaling pathway.

摘要

神经胶质瘤是最常见的原发性人类恶性脑肿瘤,最近越来越多的研究表明,只有一小部分被称为神经胶质瘤干细胞的胶质瘤细胞具有真正的肿瘤形成潜力。同时,有报道称 JMJD6 蛋白的过表达与多种肿瘤的发生和发展密切相关,并且 JMJD6 是胚胎发生过程中多个器官、组织和细胞分化所必需的。然而,目前尚不清楚 JMJD6 过表达对神经胶质瘤发展的影响。因此,为了探讨 JMJD6 表达对神经胶质瘤的影响,我们首先通过 CD133 微珠试剂盒分离神经胶质瘤干细胞,并通过神经球形成试验和免疫荧光染色进行鉴定。同时,我们通过 MTT、Transwell 测定和 Cignal finder 癌症 10 通路报告基因阵列研究了 JMJD6 对神经胶质瘤干细胞增殖、迁移和侵袭的影响及其机制。结果表明,神经胶质瘤神经球细胞阳性表达干细胞标志物 SOX2、神经外胚层干细胞标志物 Nestin,在 FBS 诱导分化一周后还表达星形胶质细胞标志物 GFAP 和神经元标志物 β-tubulin III,这证明了神经胶质瘤神经球细胞具有自我更新和多能分化能力。此外,shRNA 慢病毒载体介导的 JMJD6 敲低导致神经胶质瘤干细胞增殖、迁移和侵袭能力降低,其潜在的分子机制与 Wnt 信号通路减弱和 p53 信号通路增强有关。

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