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长链非编码 RNA PlncRNA-1 的上调通过激活 Notch 信号通路表明预后不良,并促进神经胶质瘤的进展。

Upregulation of lncRNA PlncRNA-1 indicates the poor prognosis and promotes glioma progression by activation of Notch signal pathway.

机构信息

Department of Neurosurgery, Affiliated Hospital of Yan'an University, Shaanxi Province, China.

Department of Neurology, Chang'an Hospital, Xi'an City, Shaanxi Province, China.

出版信息

Biomed Pharmacother. 2018 Jul;103:216-221. doi: 10.1016/j.biopha.2018.03.150. Epub 2018 Apr 24.

Abstract

Prostate cancer-up-regulated long noncoding RNA 1(PlncRNA-1) has been demonstrated to be increased in several cancers, which plays an oncogenic role in the development of cancer. However, the exact functions and molecular mechanism of PlncRNA-1 in the tumorigenesis of glioma has not been studied. In present work, we firstly identified that PlncRNA-1 expression levels were prominently augmented in glioma patient tissues and glioma cell lines compared with adjacent noncancerous tissue and normal cells, respectively. Moreover, Kaplan-Meier survival analysis indicated that glioma patients with high PlncRNA-1 expression had shorter overall survival (OS) and progression-free survival (PFS) than those with low PlncRNA-1 expression. Furthermore, loss-of-function assay showed that PlncRNA-1 knockdown dramatically reduced cell proliferation, colony formation, and promoted apoptosis of glioma cell lines. In addition, overexpression of PlncRNA-1 promoted cell proliferation, stimulated cell colony formation, and inhibited cell apoptosis in NHA cells. Mechanically, our results showed that PlncRNA-1 significantly promoted activation of the Notch signal pathway through regulation of Notch-1, Jag-1, and Hes-1 expression. Collectively, our results implied that lncRNA PlncRNA-1 may exert tumor-promoting role in the development and progression of glioma through modulation of Notch signal pathway, providing a candidate therapeutic target for patients with glioma.

摘要

前列腺癌上调长非编码 RNA1(PlncRNA-1)已被证明在多种癌症中增加,其在癌症的发展中发挥致癌作用。然而,PlncRNA-1 在神经胶质瘤发生中的确切功能和分子机制尚未研究。在本工作中,我们首先鉴定出 PlncRNA-1 的表达水平在神经胶质瘤患者组织和神经胶质瘤细胞系中明显高于相邻非癌组织和正常细胞。此外,Kaplan-Meier 生存分析表明,PlncRNA-1 高表达的神经胶质瘤患者的总生存期(OS)和无进展生存期(PFS)比 PlncRNA-1 低表达的患者更短。此外,功能丧失实验表明,PlncRNA-1 敲低显著降低神经胶质瘤细胞系的细胞增殖、集落形成,并促进细胞凋亡。此外,PlncRNA-1 的过表达促进了 NHA 细胞的细胞增殖、刺激细胞集落形成,并抑制了细胞凋亡。机制上,我们的结果表明 PlncRNA-1 通过调节 Notch-1、Jag-1 和 Hes-1 的表达,显著促进 Notch 信号通路的激活。总之,我们的结果表明,lncRNA PlncRNA-1 可能通过调节 Notch 信号通路在神经胶质瘤的发展和进展中发挥促肿瘤作用,为神经胶质瘤患者提供了一个候选治疗靶点。

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