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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 orcid ; Persson, Helena LU orcid ; 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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
article number
35664
publisher
Nature Publishing Group
external identifiers
  • pmid:27752128
  • wos:000385584700001
  • scopus:84992027415
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
2025-10-14 09:27:20
@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>}},
  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}},
  doi          = {{10.1038/srep35664}},
  volume       = {{6}},
  year         = {{2016}},
}