1. Cancer Biology
  2. Stem Cells and Regenerative Medicine
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A long non-coding RNA targets microRNA miR-34a to regulate colon cancer stem cell asymmetric division

  1. Lihua Wang
  2. Pengcheng Bu
  3. Yiwei Ai
  4. Tara Srinivasan
  5. Huanhuan Joyce Chen
  6. Kun Xiang
  7. Steven M Lipkin
  8. Xiling Shen  Is a corresponding author
  1. Cornell University, United States
  2. Duke University, United States
  3. Weill Corenll Medical College, United States
  4. Weill Cornell Medical College, United States
Research Article
  • Cited 51
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Cite this article as: eLife 2016;5:e14620 doi: 10.7554/eLife.14620

Abstract

The roles of long non-coding RNAs (lncRNAs) in regulating cancer and stem cells are being increasingly appreciated. Its diverse mechanisms provide the regulatory network with a bigger repertoire to increase complexity. Here we report a novel LncRNA, Lnc34a, that is enriched in colon cancer stem cells (CCSCs) and initiates asymmetric division by directly targeting the microRNA miR-34a to cause its spatial imbalance. Lnc34a recruits Dnmt3a via PHB2 and HDAC1 to methylate and deacetylate the miR-34a promoter simultaneously, hence epigenetically silencing miR-34a expression independent of its upstream regulator, p53. Lnc34a levels affect CCSC self-renewal and colorectal cancer (CRC) growth in xenograft models. Lnc34a is upregulated in late-stage CRCs, contributing to epigenetic miR-34a silencing and CRC proliferation. The fact that lncRNA targets microRNA highlights the regulatory complexity of non-coding RNAs (ncRNAs), which occupy the bulk of the genome.

Article and author information

Author details

  1. Lihua Wang

    Department of Biological and Environmental Engineering, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Pengcheng Bu

    Department of Biomedical Engineering, Duke University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yiwei Ai

    Department of Biomedical Engineering, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Tara Srinivasan

    Department of Biomedical Engineering, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Huanhuan Joyce Chen

    Meyer Cancer Center, Weill Corenll Medical College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Kun Xiang

    Department of Biomedical Engineering, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Steven M Lipkin

    Deparments of Medicine, Genetic Medicine and Surgery, Weill Cornell Medical College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Xiling Shen

    Department of Biomedical Engineering, Duke University, Durham, United States
    For correspondence
    xs37@duke.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animal experiments were approved by The Cornell Center for Animal Resources and Education (CARE) and followed the protocol (2009-0071 and 2010-0100).

Human subjects: Frozen CRC specimens of different clinical stages were acquired from Weill Cornell Medical College (WCMC) Colon Cancer Biobank. The studies followed informed consent and approval of the IRB committee at Weill Cornell Medical College.

Reviewing Editor

  1. Michael R Green, Howard Hughes Medical Institute, University of Massachusetts Medical School, United States

Publication history

  1. Received: January 21, 2016
  2. Accepted: April 13, 2016
  3. Accepted Manuscript published: April 14, 2016 (version 1)
  4. Version of Record published: May 6, 2016 (version 2)

Copyright

© 2016, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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