Gene coexpression networks reveal a broad role for lncRNAs in inflammatory bowel disease.

Autor:	Johnson JL; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA., Sargsyan D; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA., Neiman EM; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA., Hart A; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA., Stojmirovic A; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA., Kosoy R; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, Icahn Institute for Data Science and Genomic Technology, New York, New York, USA., Irizar H; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, Icahn Institute for Data Science and Genomic Technology, New York, New York, USA., Suárez-Fariñas M; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, Icahn Institute for Data Science and Genomic Technology, New York, New York, USA.; Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Song WM; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, Icahn Institute for Data Science and Genomic Technology, New York, New York, USA., Argmann C; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, Icahn Institute for Data Science and Genomic Technology, New York, New York, USA., Avey S; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA., Shmuel-Galia L; Program in Innate Immunity, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA., Vierbuchen T; Program in Innate Immunity, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA., Bongers G; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA., Sun Y; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA., Edelstein L; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA., Perrigoue J; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA., Towne JE; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA., Hall AO; Immunology Translational Early Development, Bristol Myers Squibb, Summit, New Jersey, USA., Fitzgerald KA; Program in Innate Immunity, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA., Hoebe K; Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2024 Feb 08; Vol. 9 (3). Date of Electronic Publication: 2024 Feb 08.
DOI:	10.1172/jci.insight.168988
Abstrakt:	The role of long noncoding RNAs (lncRNAs) in disease is incompletely understood, but their regulation of inflammation is increasingly appreciated. We addressed the extent of lncRNA involvement in inflammatory bowel disease (IBD) using biopsy-derived RNA-sequencing data from a large cohort of deeply phenotyped patients with IBD. Weighted gene correlation network analysis revealed gene modules of lncRNAs coexpressed with protein-coding genes enriched for biological pathways, correlated with epithelial and immune cell signatures, or correlated with distal colon expression. Correlation of modules with clinical features uncovered a module correlated with disease severity, with an enriched interferon response signature containing the hub lncRNA IRF1-AS1. Connecting genes to IBD-associated single nucleotide polymorphisms (SNPs) revealed an enrichment of SNP-adjacent lncRNAs in biologically relevant modules. Ulcerative colitis-specific SNPs were enriched in distal colon-related modules, suggesting that disease-specific mechanisms may result from altered lncRNA expression. The function of the IBD-associated SNP-adjacent lncRNA IRF1-AS1 was explored in human myeloid cells, and our results suggested IRF1-AS1 promoted optimal production of TNF-α, IL-6, and IL-23. A CRISPR/Cas9-mediated activation screen in THP-1 cells revealed several lncRNAs that modulated LPS-induced TNF-α responses. Overall, this study uncovered the expression patterns of lncRNAs in IBD that identify functional, disease-relevant lncRNAs.
Databáze:	MEDLINE
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