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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


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Volume 395, Issue 9

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Kallikreins are involved in an miRNA network that contributes to prostate cancer progression

Sara Samaan
  • Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, 30 Bond Street, Toronto M5B 1W8, Canada
  • Other articles by this author:
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/ Zsuzsanna Lichner
  • Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, 30 Bond Street, Toronto M5B 1W8, Canada
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/ Qiang Ding
  • Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, 30 Bond Street, Toronto M5B 1W8, Canada
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/ Carol Saleh
  • Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, 30 Bond Street, Toronto M5B 1W8, Canada
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/ Joseph Samuel
  • Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, 30 Bond Street, Toronto M5B 1W8, Canada
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/ Catherine Streutker
  • Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, 30 Bond Street, Toronto M5B 1W8, Canada
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada
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/ George M. Yousef
  • Corresponding author
  • Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, 30 Bond Street, Toronto M5B 1W8, Canada
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada
  • Email
  • Other articles by this author:
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Published Online: 2014-08-06 | DOI: https://doi.org/10.1515/hsz-2013-0288

Abstract

MicroRNAs (miRNAs) are short RNA nucleotides that negatively regulate their target genes. They are differentially expressed in prostate cancer. Kallikreins are genes that encode serine proteases and are dysregulated in cancer. We elucidated a miRNA-kallikrein network that can be involved in prostate cancer progression. Target prediction identified 23 miRNAs that are dysregulated between high and low risk biochemical failure and are predicted to target five kallikreins linked to prostate cancer; KLK2, KLK3, KLK4, KLK14 and KLK15. We also identified 14 miRNAs that are differentially expressed between Gleason grades and are predicted to target these kallikreins. This demonstrates that kallikreins are downstream effectors through which miRNAs influence tumor progression. We show, through in-silico and experimental analysis, that miR-378/422a and its gene targets PIK3CG, GRB2, AKT3, KLK4 and KLK14 form an integrated circuit in prostate cancer. Our analysis shows that a minisatellite sequence in the kallikrein locus consists of a number of microsatellite repeats that represent predicted miRNA response elements. A number of kallikrein and non-kallikrein prostate cancer-related genes share these microsatellite repeats. We validated some of these interactions in prostate cancer cell lines. Finally, we provide preliminary evidence on the presence of a miRNA-mediated cross-talk between kallikreins, including a kallikrein pseudogene.

Keywords: biochemical failure; Gleason grade; microsatellite repeat; personalized medicine; prostate-specific antigen; tumor markers

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About the article

Corresponding author: George M. Yousef, Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, 30 Bond Street, Toronto M5B 1W8, Canada; and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada, e-mail:


Received: 2013-11-29

Accepted: 2014-05-26

Published Online: 2014-08-06

Published in Print: 2014-09-01


Citation Information: Biological Chemistry, Volume 395, Issue 9, Pages 991–1001, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2013-0288.

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