Long non-coding RNA PVT1 predicts poor prognosis and induces radioresistance by regulating DNA repair and cell apoptosis in nasopharyngeal carcinoma

Yi He,Yizhou Jing,Can Guo,Jia Luo,Fang Wei,Qianjin Liao,Zhaoyang Zeng,Qianxi Ni,Ming Zhou,Pei Yang,Xiaoling Li,Guiyuan Li,Fang Xiong,Wei Xiong,Yanyan Tang,Yong Li,Jinmeng Pang,Bo Xiang,Liting Yang

doi:10.1038/s41419-018-0265-y

Abstract

The long non-coding RNA, plasmacytoma variant translocation 1 (PVT1), is highly expressed in a variety of tumors, and is believed to be a potential oncogene. However, the role and mechanism of action of PVT1 in the carcinogenesis and progression of nasopharyngeal carcinomas (NPCs) remains unclear. In this study, for the first time, we have discovered that PVT1 shows higher expression in NPCs than in normal nasopharyngeal epithelial tissue, and patients with NPCs who show higher expression of PVT1 have worse progression-free and overall survivals. Additionally, we observed that the proliferation of NPC cells decreased, and their rate of apoptosis increased; these results indicated that the knockdown of PVT1 expression in the NPC cells induced radiosensitivity. Further, we have shown that the knockdown of PVT1 expression can induce apoptosis in the NPC cells by influencing the DNA damage repair pathway after radiotherapy. In general, our study shows that PVT1 may be a novel biomarker for prognosis and a new target for the treatment of NPCs. Additionally, targeting PVT1 may be a potential strategy for the clinical management of NPC and for the improvement of the curative effect of radiation in NPCs.

Highlights

Nasopharyngeal carcinoma (NPC) is a malignant tumor arising from nasopharyngeal epithelial (NPE) cells[1,2,3]
We have found that plasmacytoma variant translocation 1 (PVT1) is highly expressed in patients with NPC and is related to poor relapse-free survival (RFS) and overall survivals (OS) of these patients
Among the differentially expressed long non-coding RNAs (lncRNAs), PVT1 was highly expressed in the NPC samples in all three above-mentioned datasets (Fig. 1a–c)

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is a malignant tumor arising from nasopharyngeal epithelial (NPE) cells[1,2,3]. Many studies have investigated the mechanisms of radioresistance, such as DNA damage[14], tumor stem cells[15,16], and autophagy[17,18]. Official journal of the Cell Death Differentiation Association He et al Cell Death and Disease (2018)9:235 radioresistance due to DNA damage has been extensively studied. The damaged DNA is identified by many proteins; some of these bind with the damaged DNA to mask these damaged areas, which are not recognized by the repair system, and this process eventually leads to cell apoptosis. Studies have shown that lncRNAs are involved in DNA damage repair[25,26,27] and can regulate the differentiation of stem cells[28]. These studies suggest that lncRNA may be new potential molecular targets for radiosensitivity

Methods

Results

Conclusion