Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3

Elife. 2017 Jun 5;6:e23244. doi: 10.7554/eLife.23244.

Abstract

Thousands of long noncoding RNAs (lncRNAs) have been discovered, yet the function of the vast majority remains unclear. Here, we show that a p53-regulated lncRNA which we named PINCR (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a prosurvival function in human colorectal cancer cells (CRC) in vitro and tumor growth in vivo. Targeted deletion of PINCR in CRC cells significantly impaired G1 arrest and induced hypersensitivity to chemotherapeutic drugs. PINCR regulates the induction of a subset of p53 targets involved in G1 arrest and apoptosis, including BTG2, RRM2B and GPX1. Using a novel RNA pulldown approach that utilized endogenous S1-tagged PINCR, we show that PINCR associates with the enhancer region of these genes by binding to RNA-binding protein Matrin 3 that, in turn, associates with p53. Our findings uncover a critical prosurvival function of a p53/PINCR/Matrin 3 axis in response to DNA damage in CRC cells.

Keywords: DNA damage; Matrin 3; PINCR; RP3-326I13.1; cancer biology; human; lncRNA; p53.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / pathology*
  • DNA Damage*
  • Gene Expression Regulation*
  • Humans
  • Nuclear Matrix-Associated Proteins / metabolism*
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • MATR3 protein, human
  • Nuclear Matrix-Associated Proteins
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • Tumor Suppressor Protein p53