Advanced

The HER2-Encoded miR-4728-3p Regulates ESR1 through a Non-Canonical Internal Seed Interaction.

Newie, Inga LU ; Sökilde, Rolf LU ; Persson, Helena LU ; Grabau, Dorthe LU ; Rego, Natalia; Kvist, Anders LU ; von Stedingk, Kristoffer LU ; Axelson, Håkan LU ; Borg, Åke LU and Vallon-Christersson, Johan LU , et al. (2014) In PLoS ONE 9(5).
Abstract
Since the early 1980s remarkable progress has been made in understanding the role of the HER2 locus in carcinogenesis, but many details of its regulatory network are still elusive. We recently reported the finding of 367 new human microRNA (miRNA) genes of which one, mir-4728, is encoded in an intron of the HER2 gene. Here, we confirm that the HER2 oncogene is a bi-functional locus encoding the membrane receptor and a functional miRNA gene. We further show that miR-4728-3p has alternative functionalities depending on the region used for interaction with its target; the canonical seed between nucleotides 2-8 or a novel, more internal seed shifted to nucleotides 6-12. Analysis of public data shows that this internal seed region, although... (More)
Since the early 1980s remarkable progress has been made in understanding the role of the HER2 locus in carcinogenesis, but many details of its regulatory network are still elusive. We recently reported the finding of 367 new human microRNA (miRNA) genes of which one, mir-4728, is encoded in an intron of the HER2 gene. Here, we confirm that the HER2 oncogene is a bi-functional locus encoding the membrane receptor and a functional miRNA gene. We further show that miR-4728-3p has alternative functionalities depending on the region used for interaction with its target; the canonical seed between nucleotides 2-8 or a novel, more internal seed shifted to nucleotides 6-12. Analysis of public data shows that this internal seed region, although rare compared to the far more abundant canonical 2-8 seed interaction, can also direct targeted down-regulation by other miRNAs. Through the internal seed, miR-4728-3p regulates expression of estrogen receptor alpha, an interaction that would have remained undetected if classic rules for miRNA-target interaction had been applied. In summary, we present here an alternative mode of miRNA regulation and demonstrate this dual function of the HER2 locus, linking the two major biomarkers in breast cancer. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
9
issue
5
publisher
Public Library of Science
external identifiers
  • pmid:24828673
  • wos:000336857400063
  • scopus:84901353391
ISSN
1932-6203
DOI
10.1371/journal.pone.0097200
language
English
LU publication?
yes
id
97662846-7d28-4446-97cc-d0b140c3ed24 (old id 4455195)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24828673?dopt=Abstract
date added to LUP
2014-06-04 20:23:47
date last changed
2017-08-13 04:06:19
@article{97662846-7d28-4446-97cc-d0b140c3ed24,
  abstract     = {Since the early 1980s remarkable progress has been made in understanding the role of the HER2 locus in carcinogenesis, but many details of its regulatory network are still elusive. We recently reported the finding of 367 new human microRNA (miRNA) genes of which one, mir-4728, is encoded in an intron of the HER2 gene. Here, we confirm that the HER2 oncogene is a bi-functional locus encoding the membrane receptor and a functional miRNA gene. We further show that miR-4728-3p has alternative functionalities depending on the region used for interaction with its target; the canonical seed between nucleotides 2-8 or a novel, more internal seed shifted to nucleotides 6-12. Analysis of public data shows that this internal seed region, although rare compared to the far more abundant canonical 2-8 seed interaction, can also direct targeted down-regulation by other miRNAs. Through the internal seed, miR-4728-3p regulates expression of estrogen receptor alpha, an interaction that would have remained undetected if classic rules for miRNA-target interaction had been applied. In summary, we present here an alternative mode of miRNA regulation and demonstrate this dual function of the HER2 locus, linking the two major biomarkers in breast cancer.},
  articleno    = {e97200},
  author       = {Newie, Inga and Sökilde, Rolf and Persson, Helena and Grabau, Dorthe and Rego, Natalia and Kvist, Anders and von Stedingk, Kristoffer and Axelson, Håkan and Borg, Åke and Vallon-Christersson, Johan and Rovira, Carlos},
  issn         = {1932-6203},
  language     = {eng},
  number       = {5},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {The HER2-Encoded miR-4728-3p Regulates ESR1 through a Non-Canonical Internal Seed Interaction.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0097200},
  volume       = {9},
  year         = {2014},
}