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

• DOI: 10.1172/jci.insight.168988
• Publication Date: 2024-03-05T17:02:33Z
• Authors: John L. Johnson; Davit Sargsyan; Eric M. Neiman; Amy Hart; Aleksandar Stojmi...; Roman Kosoy; Haritz Irizar; Mayte Suárez-Fariñas; Won-Min Song; Carmen Argmann; Stefan Avey; Liraz Shmuel-Galia; Tim Vierbuchen; Gerold Bongers; Yu Sun; Leonard Edelstein; Jacqueline Perrigoue; Jennifer E. Towne; Aisling O’Hara Hall; Katherine A. Fitz...; Kasper Hoebe
• Keywords: SNP; IRF1

The role of long noncoding RNAs (lncRNAs) in disease is incompletely understood, but their regulation inflammation increasingly appreciated. We addressed the extent lncRNA involvement inflammatory bowel (IBD) using biopsy-derived RNA-sequencing data from a large cohort deeply phenotyped patients with IBD. Weighted gene correlation network analysis revealed modules lncRNAs coexpressed protein-coding genes enriched for biological pathways, correlated epithelial and immune cell signatures, or distal colon expression. Correlation clinical features uncovered module severity, an interferon response signature containing hub IRF1-AS1. Connecting to IBD-associated single nucleotide polymorphisms (SNPs) enrichment SNP-adjacent biologically relevant modules. Ulcerative colitis–specific SNPs were colon–related modules, suggesting that disease-specific mechanisms may result altered function IRF1-AS1 was explored human myeloid cells, our results suggested promoted optimal production TNF-α, IL-6, IL-23. A CRISPR/Cas9-mediated activation screen THP-1 cells several modulated LPS-induced TNF-α responses. Overall, this study expression patterns IBD identify functional, disease-relevant lncRNAs.