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Subtype and cell type specific expression of lncRNAs provide insight into breast cancer

Bjørklund, Sunniva Stordal ; Aure, Miriam Ragle ; Häkkinen, Jari LU orcid ; Vallon-Christersson, Johan LU orcid ; Kumar, Surendra ; Evensen, Katrine Bull ; Fleischer, Thomas ; Tost, Jörg ; Sahlberg, Kristine K. and Mathelier, Anthony , et al. (2022) In Communications Biology 5(1).
Abstract

Long non-coding RNAs (lncRNAs) are involved in breast cancer pathogenesis through chromatin remodeling, transcriptional and post-transcriptional gene regulation. We report robust associations between lncRNA expression and breast cancer clinicopathological features in two population-based cohorts: SCAN-B and TCGA. Using co-expression analysis of lncRNAs with protein coding genes, we discovered three distinct clusters of lncRNAs. In silico cell type deconvolution coupled with single-cell RNA-seq analyses revealed that these three clusters were driven by cell type specific expression of lncRNAs. In one cluster lncRNAs were expressed by cancer cells and were mostly associated with the estrogen signaling pathways. In the two other clusters,... (More)

Long non-coding RNAs (lncRNAs) are involved in breast cancer pathogenesis through chromatin remodeling, transcriptional and post-transcriptional gene regulation. We report robust associations between lncRNA expression and breast cancer clinicopathological features in two population-based cohorts: SCAN-B and TCGA. Using co-expression analysis of lncRNAs with protein coding genes, we discovered three distinct clusters of lncRNAs. In silico cell type deconvolution coupled with single-cell RNA-seq analyses revealed that these three clusters were driven by cell type specific expression of lncRNAs. In one cluster lncRNAs were expressed by cancer cells and were mostly associated with the estrogen signaling pathways. In the two other clusters, lncRNAs were expressed either by immune cells or fibroblasts of the tumor microenvironment. To further investigate the cis-regulatory regions driving lncRNA expression in breast cancer, we identified subtype-specific transcription factor (TF) occupancy at lncRNA promoters. We also integrated lncRNA expression with DNA methylation data to identify long-range regulatory regions for lncRNA which were validated using ChiA-Pet-Pol2 loops. lncRNAs play an important role in shaping the gene regulatory landscape in breast cancer. We provide a detailed subtype and cell type-specific expression of lncRNA, which improves the understanding of underlying transcriptional regulation in breast cancer.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Communications Biology
volume
5
issue
1
article number
834
publisher
Nature Publishing Group
external identifiers
  • pmid:35982125
  • scopus:85136095458
ISSN
2399-3642
DOI
10.1038/s42003-022-03559-7
language
English
LU publication?
yes
id
f9814373-6038-4802-be1f-18f305cf9c19
date added to LUP
2022-10-20 16:50:19
date last changed
2024-04-18 15:54:24
@article{f9814373-6038-4802-be1f-18f305cf9c19,
  abstract     = {{<p>Long non-coding RNAs (lncRNAs) are involved in breast cancer pathogenesis through chromatin remodeling, transcriptional and post-transcriptional gene regulation. We report robust associations between lncRNA expression and breast cancer clinicopathological features in two population-based cohorts: SCAN-B and TCGA. Using co-expression analysis of lncRNAs with protein coding genes, we discovered three distinct clusters of lncRNAs. In silico cell type deconvolution coupled with single-cell RNA-seq analyses revealed that these three clusters were driven by cell type specific expression of lncRNAs. In one cluster lncRNAs were expressed by cancer cells and were mostly associated with the estrogen signaling pathways. In the two other clusters, lncRNAs were expressed either by immune cells or fibroblasts of the tumor microenvironment. To further investigate the cis-regulatory regions driving lncRNA expression in breast cancer, we identified subtype-specific transcription factor (TF) occupancy at lncRNA promoters. We also integrated lncRNA expression with DNA methylation data to identify long-range regulatory regions for lncRNA which were validated using ChiA-Pet-Pol2 loops. lncRNAs play an important role in shaping the gene regulatory landscape in breast cancer. We provide a detailed subtype and cell type-specific expression of lncRNA, which improves the understanding of underlying transcriptional regulation in breast cancer.</p>}},
  author       = {{Bjørklund, Sunniva Stordal and Aure, Miriam Ragle and Häkkinen, Jari and Vallon-Christersson, Johan and Kumar, Surendra and Evensen, Katrine Bull and Fleischer, Thomas and Tost, Jörg and Sahlberg, Kristine K. and Mathelier, Anthony and Bhanot, Gyan and Ganesan, Shridar and Tekpli, Xavier and Kristensen, Vessela N.}},
  issn         = {{2399-3642}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Communications Biology}},
  title        = {{Subtype and cell type specific expression of lncRNAs provide insight into breast cancer}},
  url          = {{http://dx.doi.org/10.1038/s42003-022-03559-7}},
  doi          = {{10.1038/s42003-022-03559-7}},
  volume       = {{5}},
  year         = {{2022}},
}