Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer

Int J Clin Exp Pathol. 2014 Sep 15;7(10):6929-35. eCollection 2014.

Abstract

Introduction: Non-small cell lung cancer (NSCLC) is the major cause of cancer death worldwide. Increasing evidence shows that long non coding RNAs (lncRNAs) are widely involved in the development and progression of NSCLC. lncRNA PVT1 in several cancers has been studied, its role in lung cancer remains unknown. Our studies were designed to investigate the expression, biological role and clinical significance of PVT1 in lung cancer.

Methods: lncRNA PVT1 expression in 82 NSCLC tissues and 3 lung cancer cell lines was measured by quantitative Real-time PCR (qRT-PCR). Its association with overall survival of patients was analyzed by statistical analysis. RNA interference (RNAi) approaches were used to investigate the biological functions of PVT1. The effect of PVT1 on proliferation was evaluated by MTT, cell migration and invasion ability was evaluated by cell migration and invasion assays.

Results: lncRNA PVT1 expression was significantly upregulated in NSCLC tissues and lung cancer cells when compared with corresponding adjacent normal tissues and normal bronchial epithelial cells. Increased PVT1 expression was significantly correlated with histological grade and lymph node metastasis. In addition, NSCLC patients with PVT1 higher expression have shown significantly poorer overall survival than those with lower PVT1 expression. And PVT1 expression was an independent prognostic marker of overall survival in a multivariate analysis. In vitro assays our results indicated that knockdown of PVT1 inhibited cell proliferation, migration, and invasion.

Conclusions: Our data indicated that lncRNA PVT1 is significantly upregulated in NSCLC tissues and may represent a new biomarker and a potential therapeutic target for NSCLC intervention.

Keywords: NSCLC; invasion; lncRNA PVT1; migration; prognosis; proliferation.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chi-Square Distribution
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Proportional Hazards Models
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Risk Factors
  • Time Factors
  • Transfection
  • Up-Regulation

Substances

  • PVT1 long-non-coding RNA, human
  • RNA, Long Noncoding