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HER2-encoded mir-4728 forms a receptor-independent circuit with miR-21-5p through the non-canonical poly(A) polymerase PAPD5

Author:
  • Inga Newie
  • Rolf Søkilde
  • Helena Persson
  • Thiago Jacomasso
  • Andrej Gorbatenko
  • Åke Borg
  • Michiel De Hoon
  • Stine F. Pedersen
  • Carlos Rovira
Publishing year: 2016-10-18
Language: English
Publication/Series: Scientific Reports
Volume: 6
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

We previously reported that the human HER2 gene encodes the intronic microRNA mir-4728, which is overexpressed together with its oncogenic host gene and may act independently of the HER2 receptor. More recently, we also reported that the oncogenic miR-21-5p is regulated by 3′ tailing and trimming by the non-canonical poly(A) polymerase PAPD5 and the ribonuclease PARN. Here we demonstrate a dual function for the HER2 locus in upregulation of miR-21-5p; while HER2 signalling activates transcription of mir-21, miR-4728-3p specifically stabilises miR-21-5p through inhibition of PAPD5. Our results establish a new and unexpected oncogenic role for the HER2 locus that is not currently being targeted by any anti-HER2 therapy.

Keywords

  • Cancer and Oncology
  • Cell and Molecular Biology

Other

Published
  • Cancer and non coding RNA
  • ISSN: 2045-2322
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

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Project manager

Familial Breast Cancer

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Professor

Oncology and Pathology, MV

MV 404 C21C2

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