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

  1. Ritu Chaudhary
  2. Berkley Gryder
  3. Wendy S Woods
  4. Murugan Subramanian
  5. Matthew F Jones
  6. Xiao Ling Li
  7. Lisa M Jenkins
  8. Svetlana A Shabalina
  9. Min Mo
  10. Mary Dasso
  11. Yuan Yang
  12. Lalage M Wakefield
  13. Yuelin Zhu
  14. Susan M Frier
  15. Branden S Moriarity
  16. Kannanganattu V Prasanth
  17. Pablo Perez-Pinera
  18. Ashish Lal  Is a corresponding author
  1. National Institutes of Health, United States
  2. University of Illinois at Urbana Champaign, United States
  3. Ionis Pharmaceuticals, United States
  4. University of Minnesota, United States
  5. University of Illinois at Urbana-Champaign, United States
Research Article
  • Cited 35
  • Views 2,817
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Cite this article as: eLife 2017;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.

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Article and author information

Author details

  1. Ritu Chaudhary

    Regulatory RNAs and Cancer Section, Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Berkley Gryder

    Oncogenomics Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Gaithersburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Wendy S Woods

    Department of Bioengineering, University of Illinois at Urbana Champaign, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Murugan Subramanian

    Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Matthew F Jones

    Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Xiao Ling Li

    Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Lisa M Jenkins

    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Svetlana A Shabalina

    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Min Mo

    Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Mary Dasso

    Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Yuan Yang

    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Lalage M Wakefield

    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Yuelin Zhu

    Molecular Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Susan M Frier

    Ionis Pharmaceuticals, Carlsbad, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Branden S Moriarity

    Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Kannanganattu V Prasanth

    Department of Cell and Developmental Biology, University of Illinois at Urbana Champaign, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Pablo Perez-Pinera

    Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
  18. Ashish Lal

    Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
    For correspondence
    ashish.lal@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4299-8177

Funding

National Cancer Institute (NIH IRP)

  • Ashish Lal

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal studies were conducted under protocol LC-070 approved by the Animal Care and Use Committee of the National Cancer Institute, The Frederick National Laboratory and the Center for Cancer Research are accredited by AALAC International and follow the Public Health Service Policy for the Care and Use of Laboratory Animals.

Reviewing Editor

  1. Joaquín M Espinosa, University of Colorado School of Medicine, United States

Publication history

  1. Received: November 12, 2016
  2. Accepted: May 20, 2017
  3. Accepted Manuscript published: June 5, 2017 (version 1)
  4. Version of Record published: June 14, 2017 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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