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

Cell Death Dis. 2018 Feb 14;9(2):235. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Repair*
  • DNA, Neoplasm / genetics*
  • DNA, Neoplasm / metabolism
  • Databases, Genetic
  • Follow-Up Studies
  • Gamma Rays / therapeutic use
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Nasopharyngeal Carcinoma / diagnosis
  • Nasopharyngeal Carcinoma / genetics*
  • Nasopharyngeal Carcinoma / mortality
  • Nasopharyngeal Carcinoma / therapy
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Radiation Tolerance / genetics
  • Signal Transduction
  • Survival Analysis

Substances

  • DNA, Neoplasm
  • MYC protein, human
  • PVT1 long-non-coding RNA, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Poly(ADP-ribose) Polymerases
  • Caspases