Subtype and cell type specific expression of lncRNAs provide insight into breast cancer
Sunniva Stordal Bjørklund, Miriam Ragle Aure, Jari Häkkinen, Johan Vallon-Christersson, Surendra Kumar, Katrine Bull Evensen, Thomas Fleischer, Jörg Tost, OSBREAC, Kristine K Sahlberg, Anthony Mathelier, Gyan Bhanot, Shridar Ganesan, Xavier Tekpli, Vessela N Kristensen, Tone F Bathen, Elin Borgen, Anne-Lise Børresen-Dale, Olav Engebråten, Britt Fritzman, Olaf Johan Hartmann-Johnsen, Øystein Garred, Jürgen Geisler, Gry Aarum Geitvik, Solveig Hofvind, Rolf Kåresen, Anita Langerød, Ole Christian Lingjærde, Gunhild Mari Mælandsmo, Bjørn Naume, Hege G Russnes, Torill Sauer, Helle Kristine Skjerven, Ellen Schlichting, Therese Sørlie, Sunniva Stordal Bjørklund, Miriam Ragle Aure, Jari Häkkinen, Johan Vallon-Christersson, Surendra Kumar, Katrine Bull Evensen, Thomas Fleischer, Jörg Tost, OSBREAC, Kristine K Sahlberg, Anthony Mathelier, Gyan Bhanot, Shridar Ganesan, Xavier Tekpli, Vessela N Kristensen, Tone F Bathen, Elin Borgen, Anne-Lise Børresen-Dale, Olav Engebråten, Britt Fritzman, Olaf Johan Hartmann-Johnsen, Øystein Garred, Jürgen Geisler, Gry Aarum Geitvik, Solveig Hofvind, Rolf Kåresen, Anita Langerød, Ole Christian Lingjærde, Gunhild Mari Mælandsmo, Bjørn Naume, Hege G Russnes, Torill Sauer, Helle Kristine Skjerven, Ellen Schlichting, Therese Sørlie
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, 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.
Conflict of interest statement
The authors declare no competing interests.
© 2022. The Author(s).
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References
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