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长链非编码 RNA PVT1 表明神经胶质瘤预后不良,并通过靶向 EZH2 促进细胞增殖和侵袭。

Long non-coding RNA PVT1 indicates a poor prognosis of glioma and promotes cell proliferation and invasion via target EZH2.

机构信息

Department of Neurosurgery, School of Medicine, Jinling Hospital, Southern Medical University (Guangzhou), 305 East Zhongshan Road, Nanjing 210002, China.

Department of Neurosurgery, The First People's Hospital of Yibin City, 65 Wenxing Road, Yibin 644000, China.

出版信息

Biosci Rep. 2017 Dec 15;37(6). doi: 10.1042/BSR20170871. Print 2017 Dec 22.

Abstract

Human glioma is one of the malignant tumors of the central nervous system (CNS). Its prognosis is poor, which is due to its genetic heterogeneity and our poor understanding of its underlying molecular mechanisms. The present study aimed to assess the relationship between plasmacytoma variant translocation 1 (PVT1) and enhancer of zeste homolog 2 (EZH2), and their effects on the proliferation and invasion of glioma cells. The expression levels of PVT1 and EZH2 in human glioma tissues and cell lines were measured using quantitative RT-PCR (qRT-PCR). Then, after siRNA-PVT1 and entire PVT1 sequence vector transfection, we determined the regulation roles of PVT1 in the proliferation, apoptosis, migration, and invasion of glioma cells. We found that the expression levels of both PVT1 and EZH2 were up-regulated in human glioma tissues and cell lines, and positively correlated with glioma malignancy. And, silencing of PVT1 expression resulted in decreased proliferation, increased apoptosis, and decreased migration and invasion. In addition, exogenous PVT1 led to increased EZH2 expression and increased proliferation and induced proliferation and invasion. These data inferred that long non-coding RNA PVT1 could be served as an indicator of glioma prognosis, and PVT1-EZH2 regulatory pathway may be a novel therapeutic target for treating glioma.

摘要

人脑胶质瘤是中枢神经系统(CNS)的恶性肿瘤之一。其预后较差,这是由于其遗传异质性和我们对其潜在分子机制的了解不足。本研究旨在评估浆细胞瘤变异易位 1(PVT1)和增强子的锌指蛋白 2(EZH2)之间的关系,及其对胶质瘤细胞增殖和侵袭的影响。采用实时定量 RT-PCR(qRT-PCR)检测人脑胶质瘤组织和细胞系中 PVT1 和 EZH2 的表达水平。然后,在转染 siRNA-PVT1 和全长 PVT1 序列载体后,我们确定了 PVT1 在胶质瘤细胞增殖、凋亡、迁移和侵袭中的调节作用。我们发现 PVT1 和 EZH2 的表达水平在人胶质瘤组织和细胞系中均上调,且与胶质瘤恶性程度呈正相关。沉默 PVT1 的表达导致增殖减少、凋亡增加、迁移和侵袭减少。此外,外源性 PVT1 导致 EZH2 表达增加、增殖增加,并诱导增殖和侵袭。这些数据推断长链非编码 RNA PVT1 可作为胶质瘤预后的指标,PVT1-EZH2 调控途径可能是治疗胶质瘤的新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11f4/6435466/afa5760d702d/bsr-37-bsr20170871-g1.jpg

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