Low expression of long noncoding RNA PANDAR predicts a poor prognosis of non-small cell lung cancer and affects cell apoptosis by regulating Bcl-2

Cell Death Dis. 2015 Feb 26;6(2):e1665. doi: 10.1038/cddis.2015.30.

Abstract

Recently, a novel class of transcripts, long noncoding RNAs (lncRNAs), is involved in diseases including cancer. Here, we investigated the the role of lncRNA PANDAR in the progression of non-small cell lung carcinoma (NSCLC). PANDAR, interacting with NF-YA, was generally downregulated in NSCLC tissues. In a cohort of 140 NSCLC patients, decreased PANDAR expression was negatively correlated with greater tumor size (P<0.001) and advanced TNM stage (P=0.002). Moreover, PANDAR could serve as an independent predictor for overall survival in NSCLC (P=0.015). Further experiments demonstrated that PANDAR expression was induced by p53, and chromatin immunoprecipitation (ChIP) assays confirmed that PANDAR was a direct transcriptional target of p53 in NSCLC cells. PANDAR overexpression significantly repressed the proliferation in vitro and in vivo. We also showed that PANDAR-mediated growth regulation is in part due to the transcriptional modulation of Bcl-2 by interacting with NF-YA, thus affecting NSCLC cell apoptosis. To our knowledge, this is the first report which showed the role of PANDAR in the progression of NSCLC. The p53/PANDAR/NF-YA/Bcl-2 interaction might serve as targets for NSCLC diagnosis and therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / physiology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Humans
  • In Vitro Techniques
  • Multivariate Analysis
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Long Noncoding / genetics*

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Long Noncoding