Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer

Nat Commun. 2016 Mar 15;7:10982. doi: 10.1038/ncomms10982.

Abstract

Mounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. However, the prevalence, functional significance and targets of lncRNA-mediated sponge regulation of cancer are mostly unknown. Here we identify a lncRNA-mediated sponge regulatory network that affects the expression of many protein-coding prostate cancer driver genes, by integrating analysis of sequence features and gene expression profiles of both lncRNAs and protein-coding genes in tumours. We confirm the tumour-suppressive function of two lncRNAs (TUG1 and CTB-89H12.4) and their regulation of PTEN expression in prostate cancer. Surprisingly, one of the two lncRNAs, TUG1, was previously known for its function in polycomb repressive complex 2 (PRC2)-mediated transcriptional regulation, suggesting its sub-cellular localization-dependent function. Our findings not only suggest an important role of lncRNA-mediated sponge regulation in cancer, but also underscore the critical influence of cytoplasmic localization on the efficacy of a sponge lncRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Blotting, Western
  • Cell Fractionation
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Regulatory Networks
  • HCT116 Cells
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • MicroRNAs
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Polycomb Repressive Complex 2
  • Prostatic Neoplasms / genetics*
  • RNA Transport / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • TUG1 long noncoding RNA, human
  • Polycomb Repressive Complex 2
  • PTEN Phosphohydrolase
  • PTEN protein, human