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

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: SC...

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Autores principales: Bjørklund, Sunniva Stordal, Aure, Miriam Ragle, Häkkinen, Jari, Vallon-Christersson, Johan, Kumar, Surendra, Evensen, Katrine Bull, Fleischer, Thomas, Tost, Jörg, Sahlberg, Kristine K., Mathelier, Anthony, Bhanot, Gyan, Ganesan, Shridar, Tekpli, Xavier, Kristensen, Vessela N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388662/
https://www.ncbi.nlm.nih.gov/pubmed/35982125
http://dx.doi.org/10.1038/s42003-022-03559-7
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author Bjørklund, Sunniva Stordal
Aure, Miriam Ragle
Häkkinen, Jari
Vallon-Christersson, Johan
Kumar, Surendra
Evensen, Katrine Bull
Fleischer, Thomas
Tost, Jörg
Sahlberg, Kristine K.
Mathelier, Anthony
Bhanot, Gyan
Ganesan, Shridar
Tekpli, Xavier
Kristensen, Vessela N.
author_facet Bjørklund, Sunniva Stordal
Aure, Miriam Ragle
Häkkinen, Jari
Vallon-Christersson, Johan
Kumar, Surendra
Evensen, Katrine Bull
Fleischer, Thomas
Tost, Jörg
Sahlberg, Kristine K.
Mathelier, Anthony
Bhanot, Gyan
Ganesan, Shridar
Tekpli, Xavier
Kristensen, Vessela N.
author_sort Bjørklund, Sunniva Stordal
collection PubMed
description 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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spelling pubmed-93886622022-08-20 Subtype and cell type specific expression of lncRNAs provide insight into breast cancer Bjørklund, Sunniva Stordal Aure, Miriam Ragle Häkkinen, Jari Vallon-Christersson, Johan Kumar, Surendra Evensen, Katrine Bull Fleischer, Thomas Tost, Jörg Sahlberg, Kristine K. Mathelier, Anthony Bhanot, Gyan Ganesan, Shridar Tekpli, Xavier Kristensen, Vessela N. Commun Biol Article 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. Nature Publishing Group UK 2022-08-18 /pmc/articles/PMC9388662/ /pubmed/35982125 http://dx.doi.org/10.1038/s42003-022-03559-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bjørklund, Sunniva Stordal
Aure, Miriam Ragle
Häkkinen, Jari
Vallon-Christersson, Johan
Kumar, Surendra
Evensen, Katrine Bull
Fleischer, Thomas
Tost, Jörg
Sahlberg, Kristine K.
Mathelier, Anthony
Bhanot, Gyan
Ganesan, Shridar
Tekpli, Xavier
Kristensen, Vessela N.
Subtype and cell type specific expression of lncRNAs provide insight into breast cancer
title Subtype and cell type specific expression of lncRNAs provide insight into breast cancer
title_full Subtype and cell type specific expression of lncRNAs provide insight into breast cancer
title_fullStr Subtype and cell type specific expression of lncRNAs provide insight into breast cancer
title_full_unstemmed Subtype and cell type specific expression of lncRNAs provide insight into breast cancer
title_short Subtype and cell type specific expression of lncRNAs provide insight into breast cancer
title_sort subtype and cell type specific expression of lncrnas provide insight into breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388662/
https://www.ncbi.nlm.nih.gov/pubmed/35982125
http://dx.doi.org/10.1038/s42003-022-03559-7
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