Tumor Biology

, Volume 37, Issue 3, pp 4127–4134 | Cite as

Long non-coding RNA PVT1 as a novel biomarker for diagnosis and prognosis of non-small cell lung cancer

  • Di Cui
  • Cai-Hua Yu
  • Min Liu
  • Qing-Qing Xia
  • Yu-Feng Zhang
  • Wei-Long Jiang
Original Article


Accumulating evidence has indicated that long non-coding RNA PVT1 is upregulated in various human cancers. However, it remains unclear whether PVT1 is involved in the development and progression of non-small cell lung cancer (NSCLC). The present study was designed to investigate the expression, biological role, and clinical significance of PVT1 in NSCLC. Our results indicated that PVT1 expression was significantly increased in NSCLC tissues and cell lines, and its upregulation was associated with advanced T-stage and tumor–node–metastasis (TNM) stage and regional lymph node metastasis. PVT1 expression levels were robust in differentiating NSCLC tissues from controls. Kaplan–Meier curve and Cox regression analysis showed that high expression of PVT1 was associated with poor overall survival and disease-free survival in NSCLC patients. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays indicated that knockdown of PVT1 remarkably inhibited NSCLC cell proliferation, whereas overexpression of PVT1 significantly promoted cellular proliferation. In addition, PVT1 knockdown increased the number of cells in the G0/G1 phase and reduced the number of cells in the S phase, while overexpression of PVT1 could promote cell cycle progression. Furthermore, our findings also revealed that the messenger RNA (mRNA) and protein expression of P15 and P21 was significantly upregulated in NSCLC cells transfected with PVT1 small interfering RNA (siRNA) and downregulated in cells transfected with pcDNA3.1-PVT1. In conclusion, our study demonstrated that PVT1 might serve as a promising biomarker for diagnosis and prognosis of NSCLC, and it could promote the proliferation of NSCLC cells by downregulating p15 and p21 expression.


PVT1 Non-small cell lung cancer Biomarker Proliferation 


Compliance with ethical standards

Conflicts of interest



  1. 1.
    Bunn Jr PA. Early-stage non-small-cell lung cancer: current perspectives in combined-modality therapy. Clin Lung Cancer. 2004;6:85–98.CrossRefPubMedGoogle Scholar
  2. 2.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.CrossRefPubMedGoogle Scholar
  3. 3.
    Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12:861–74.CrossRefPubMedGoogle Scholar
  5. 5.
    Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Tu ZQ, Li RJ, Mei JZ, Li XH. Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma. Int J Clin Exp Pathol. 2014;7:4303–9.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Yan TH, Lu SW, Huang YQ, Que GB, Chen JH, Chen YP, et al. Upregulation of the long noncoding RNA HOTAIR predicts recurrence in stage Ta/T1 bladder cancer. Tumour Biol. 2014;35:10249–57.CrossRefPubMedGoogle Scholar
  8. 8.
    Ren S, Liu Y, Xu W, Sun Y, Lu J, Wang F, et al. Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. J Urol. 2013;190:2278–87.CrossRefPubMedGoogle Scholar
  9. 9.
    Colombo T, Farina L, Macino G, Paci P. PVT1: a rising star among oncogenic long noncoding RNAs. Biomed Res Int. 2015;2015:304208.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Wang F, Yuan JH, Wang SB, Yang F, Yuan SX, Ye C, et al. Oncofetal long noncoding RNA PVT1 promotes proliferation and stem cell-like property of hepatocellular carcinoma cells by stabilizing NOP2. Hepatology. 2014;60:1278–90.CrossRefPubMedGoogle Scholar
  11. 11.
    Takahashi Y, Sawada G, Kurashige J, Uchi R, Matsumura T, Ueo H, et al. Amplification of PVT1is involved in poor prognosis via apoptosis inhibition in colorectal cancers. Br J Cancer. 2013;110:164–71.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Guan Y, Kuo WL, Stilwell JL, Takano H, Lapuk AV, Fridlyand J, et al. Amplification of PVT1 contributes to the pathophysiology of ovarian and breast cancer. Clin Cancer Res. 2007;13:5745–55.CrossRefPubMedGoogle Scholar
  13. 13.
    Lim S, Kaldis P. Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development. 2013;140:3079–93.CrossRefPubMedGoogle Scholar
  14. 14.
    Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995;9:1149–63.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Di Cui
    • 1
  • Cai-Hua Yu
    • 2
  • Min Liu
    • 3
  • Qing-Qing Xia
    • 1
  • Yu-Feng Zhang
    • 1
  • Wei-Long Jiang
    • 1
  1. 1.Department of RespirationJiangyin Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese MedicineJiangyinChina
  2. 2.Department of Cardiothoracic SurgeryHuzhou Central HospitalHuzhouChina
  3. 3.Department of OncologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina

Personalised recommendations