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Regulatory networks and 5' partner usage of miRNA host gene fusions in breast cancer

Hafstað, Völundur LU ; Søkilde, Rolf LU orcid ; Häkkinen, Jari LU orcid ; Larsson, Malin LU ; Vallon-Christersson, Johan LU orcid ; Rovira, Carlos LU and Persson, Helena LU orcid (2022) In International Journal of Cancer 151(1). p.95-106
Abstract

Genomic rearrangements in cancer cells can create gene fusions where the juxtaposition of two different genes leads to the production of chimeric proteins or altered gene expression through promoter-swapping. We have previously shown that fusion transcripts involving microRNA (miRNA) host genes contribute to deregulation of miRNA expression regardless of the protein-coding potential of these transcripts. Many different genes can also be used as 5' partners by a miRNA host gene in what we named recurrent miRNA-convergent fusions. Here, we have explored the properties of 5' partners in fusion transcripts that involve miRNA hosts in breast tumours from The Cancer Genome Atlas (TCGA). We hypothesised that firstly, 5' partner genes should... (More)

Genomic rearrangements in cancer cells can create gene fusions where the juxtaposition of two different genes leads to the production of chimeric proteins or altered gene expression through promoter-swapping. We have previously shown that fusion transcripts involving microRNA (miRNA) host genes contribute to deregulation of miRNA expression regardless of the protein-coding potential of these transcripts. Many different genes can also be used as 5' partners by a miRNA host gene in what we named recurrent miRNA-convergent fusions. Here, we have explored the properties of 5' partners in fusion transcripts that involve miRNA hosts in breast tumours from The Cancer Genome Atlas (TCGA). We hypothesised that firstly, 5' partner genes should belong to pathways and transcriptional programmes that reflect the tumour phenotype and secondly, there should be a selection for fusion events that shape miRNA expression to benefit the tumour cell through the known hallmarks of cancer. We found that the set of 5' partners in miRNA host fusions is non-random, with overrepresentation of highly expressed genes in pathways active in cancer including epithelial-to-mesenchymal transition, translational regulation and estrogen signalling. Furthermore, many miRNAs were upregulated in samples with host gene fusions, including established oncogenic miRNAs such as mir-21 and the mir-106b~mir-93~mir-25 cluster. To the list of mechanisms for deregulation of miRNA expression, we have added fusion transcripts that change the promoter region. We propose that this adds material for genetic selection and tumour evolution in cancer cells and that miRNA host fusions can act as tumour 'drivers'. This article is protected by copyright. All rights reserved.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Cancer
volume
151
issue
1
pages
95 - 106
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:35182081
  • scopus:85125810160
ISSN
0020-7136
DOI
10.1002/ijc.33972
language
English
LU publication?
yes
additional info
This article is protected by copyright. All rights reserved.
id
dbd9d4a3-b738-4ae8-af01-70a61d51d6a7
date added to LUP
2022-02-20 16:02:23
date last changed
2025-01-15 23:39:32
@article{dbd9d4a3-b738-4ae8-af01-70a61d51d6a7,
  abstract     = {{<p>Genomic rearrangements in cancer cells can create gene fusions where the juxtaposition of two different genes leads to the production of chimeric proteins or altered gene expression through promoter-swapping. We have previously shown that fusion transcripts involving microRNA (miRNA) host genes contribute to deregulation of miRNA expression regardless of the protein-coding potential of these transcripts. Many different genes can also be used as 5' partners by a miRNA host gene in what we named recurrent miRNA-convergent fusions. Here, we have explored the properties of 5' partners in fusion transcripts that involve miRNA hosts in breast tumours from The Cancer Genome Atlas (TCGA). We hypothesised that firstly, 5' partner genes should belong to pathways and transcriptional programmes that reflect the tumour phenotype and secondly, there should be a selection for fusion events that shape miRNA expression to benefit the tumour cell through the known hallmarks of cancer. We found that the set of 5' partners in miRNA host fusions is non-random, with overrepresentation of highly expressed genes in pathways active in cancer including epithelial-to-mesenchymal transition, translational regulation and estrogen signalling. Furthermore, many miRNAs were upregulated in samples with host gene fusions, including established oncogenic miRNAs such as mir-21 and the mir-106b~mir-93~mir-25 cluster. To the list of mechanisms for deregulation of miRNA expression, we have added fusion transcripts that change the promoter region. We propose that this adds material for genetic selection and tumour evolution in cancer cells and that miRNA host fusions can act as tumour 'drivers'. This article is protected by copyright. All rights reserved.</p>}},
  author       = {{Hafstað, Völundur and Søkilde, Rolf and Häkkinen, Jari and Larsson, Malin and Vallon-Christersson, Johan and Rovira, Carlos and Persson, Helena}},
  issn         = {{0020-7136}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{1}},
  pages        = {{95--106}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{Regulatory networks and 5' partner usage of miRNA host gene fusions in breast cancer}},
  url          = {{http://dx.doi.org/10.1002/ijc.33972}},
  doi          = {{10.1002/ijc.33972}},
  volume       = {{151}},
  year         = {{2022}},
}