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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

Newie, Inga LU ; Søkilde, Rolf LU ; Persson, Helena LU ; Jacomasso, Thiago LU ; Gorbatenko, Andrej; Borg, Åke LU ; De Hoon, Michiel; Pedersen, Stine F. and Rovira, Carlos LU (2016) In Scientific Reports 6.
Abstract

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.

Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • scopus:84992027415
  • wos:000385584700001
ISSN
2045-2322
DOI
10.1038/srep35664
language
English
LU publication?
yes
id
89c22698-07a5-4fd3-8769-1b5273315c64
date added to LUP
2016-11-14 13:20:25
date last changed
2017-10-22 05:21:54
@article{89c22698-07a5-4fd3-8769-1b5273315c64,
  abstract     = {<p>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.</p>},
  articleno    = {35664},
  author       = {Newie, Inga and Søkilde, Rolf and Persson, Helena and Jacomasso, Thiago and Gorbatenko, Andrej and Borg, Åke and De Hoon, Michiel and Pedersen, Stine F. and Rovira, Carlos},
  issn         = {2045-2322},
  language     = {eng},
  month        = {10},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {HER2-encoded mir-4728 forms a receptor-independent circuit with miR-21-5p through the non-canonical poly(A) polymerase PAPD5},
  url          = {http://dx.doi.org/10.1038/srep35664},
  volume       = {6},
  year         = {2016},
}