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

Anqiang Yang,Xiaobing Yang,Handong Wang

doi:10.1042/bsr20170871

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.

Highlights

Glioma, a malignant tumor of the central nervous system (CNS), accounts for 70% of all brain tumors each year [1]
plasmacytoma variant translocation 1 (PVT1) and enhancer of zeste homolog 2 (EZH2) were up-regulated in glioma tissues and cell lines and correlate with poor prognosis
The expressions of PVT1 and EZH2 in normal brain tissues, glioma tumor tissues, and glioma cell lines were analyzed by quantitative RT-PCR (qRT-PCR). qRT-PCR analysis demonstrated that PVT1 and EZH2 were expressed at higher levels in glioma tumor tissues and cell lines than normal brain tissues and HEB cells, and positively correlated with glioma malignancy, which mean the higher the malignant grade of glioma, the higher the PVT1 and EZH2 expression level

Summary

Introduction

A malignant tumor of the central nervous system (CNS), accounts for 70% of all brain tumors each year [1]. Long non-coding RNAs (lncRNAs), which are more than 200 bases in length and unable to be translated into proteins, have been demonstrated to play crucial roles in tumorigenesis in recent years [4]. The oncogenic effects of PVT1 have been further highlighted by more recent studies demonstrating its overexpression and amplification in multiple cancer types [6,7]. Recent study found that PVT1 contributed to tumorigenesis of thyroid cancer through recruiting enhancer of zeste homolog 2 (EZH2) [8], and promoting glioma vascular endothelial cell proliferation, migration, and angiogenesis by targetting miR-186 [9]. The functional role and molecular mechanism of PVT1 in glioma remain unclear

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Results

Conclusion