Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation

  1. Bo Cao
  2. Kebing Wang
  3. Jun-ming Liao
  4. Xiang Zhou
  5. Peng Liao
  6. Shelya X Zeng
  7. Meifang He
  8. Lianzhou Chen
  9. Yulong He
  10. Wen Li  Is a corresponding author
  11. Hua Lu  Is a corresponding author
  1. Tulane University School of Medicine, United States
  2. The First Affiliated Hospital, Sun Yat-Sen University, China
  3. The First Affiliated Hospital, Sun Yat-sen University,, China

Abstract

Increasing evidence highlights the important roles of microRNAs in mediating p53's tumor suppression functions. Here, we report miR-139-5p as another new p53 microRNA target. p53 induced the transcription of miR-139-5p, which in turn suppressed the protein levels of phosphodiesterase 4D (PDE4D), an oncogenic protein involved in multiple tumor promoting processes. Knockdown of p53 reversed these effects. Also, overexpression of miR-139-5p decreased PDE4D levels and increased cellular cAMP levels, leading to BIM-mediated cell growth arrest. Furthermore, our analysis of human colorectal tumor specimens revealed significant inverse correlation between the expression of miR-139-5p and that of PDE4D. Finally, overexpression of miR-139-5p suppressed the growth of xenograft tumors, accompanied by decrease in PDE4D and increase in BIM. These results demonstrate that p53 inactivates oncogenic PDE4D by inducing the expression of miR-139-5p.

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The following data sets were generated

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Author details

  1. Bo Cao

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kebing Wang

    Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Jun-ming Liao

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Xiang Zhou

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Peng Liao

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Shelya X Zeng

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Meifang He

    Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University,, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Lianzhou Chen

    Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University,, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Yulong He

    Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University,, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Wen Li

    Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
    For correspondence
    wenli28@163.com
    Competing interests
    The authors declare that no competing interests exist.
  11. Hua Lu

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    For correspondence
    hlu2@tulane.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9285-7209

Reviewing Editor

  1. Kevin Struhl, Harvard Medical School, United States

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 of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#4257R) of Tulane University. All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering.

Version history

  1. Received: April 19, 2016
  2. Accepted: June 29, 2016
  3. Accepted Manuscript published: July 7, 2016 (version 1)
  4. Version of Record published: July 25, 2016 (version 2)

Copyright

© 2016, Cao 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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  1. Bo Cao
  2. Kebing Wang
  3. Jun-ming Liao
  4. Xiang Zhou
  5. Peng Liao
  6. Shelya X Zeng
  7. Meifang He
  8. Lianzhou Chen
  9. Yulong He
  10. Wen Li
  11. Hua Lu
(2016)
Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation
eLife 5:e15978.
https://doi.org/10.7554/eLife.15978

Share this article

https://doi.org/10.7554/eLife.15978

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