Subtype and cell type specific expression of lncRNAs provide insight into breast cancer
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Published:2022-08-18
Issue:1
Volume:5
Page:
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ISSN:2399-3642
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Container-title:Communications Biology
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language:en
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Short-container-title:Commun Biol
Author:
Bjørklund Sunniva Stordal, Aure Miriam RagleORCID, Häkkinen JariORCID, Vallon-Christersson Johan, Kumar SurendraORCID, Evensen Katrine Bull, Fleischer ThomasORCID, Tost JörgORCID, Bathen Tone F., Borgen Elin, Børresen-Dale Anne-Lise, Engebråten Olav, Fritzman Britt, Hartmann-Johnsen Olaf Johan, Garred Øystein, Geisler Jürgen, Geitvik Gry Aarum, Hofvind Solveig, Kåresen Rolf, Langerød Anita, Lingjærde Ole Christian, Mælandsmo Gunhild Mari, Naume Bjørn, Russnes Hege G., Sauer Torill, Skjerven Helle Kristine, Schlichting Ellen, Sørlie Therese, Sahlberg Kristine K., Mathelier AnthonyORCID, Bhanot GyanORCID, Ganesan Shridar, Tekpli XavierORCID, Kristensen Vessela N.ORCID,
Abstract
AbstractLong 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.
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference72 articles.
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