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

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

Author information

1
Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States.
2
Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States.
3
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, United States.
4
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States.
5
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, United States.
6
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
7
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States.
8
Molecular Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States.
9
Ionis Pharmaceuticals, Carlsbad, United States.
10
Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Twin Cities, United States.
11
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, United States.

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

PMID:
28580901
PMCID:
PMC5470874
DOI:
10.7554/eLife.23244
[Indexed for MEDLINE]
Free PMC Article

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