The lncRNA HOXA11os regulates mitochondrial function in myeloid cells to maintain intestinal homeostasis

Shmuel-Galia, Liraz; Humphries, Fiachra; Vierbuchen, Tim; Jiang, Zhaozhao; Santos, Nuno; Johnson, John L.; Shklyar, Boris; Joannas, Leonel; Mustone, Nicholas; Sherman, Shany; Ward, Doyle V.; Houghton, JeanMarie; Baer, Christina E.; O'Hara, Aisling; Henao‐Mejia, Jorge; Hoebe, Kasper; Fitzgerald, Katherine A.

doi:10.1016/j.cmet.2023.06.019

Cited by 8 publications

(1 citation statement)

References 72 publications

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“…In addition to the functional lncRNAs identified through gene hubs or PCs, the lncRNA HOXA11-AS was adjacent to an IBD SNP and organized in the yellow module, a module highly associated with the rectum and enriched for UC-specific SNPs. We recently demonstrated the protective role of the highly conserved mouse ortholog Hoxa11os in colitis by restraining myeloid cell inflammatory cytokine production in the distal gut ( 52 ). Therefore, identifying lncRNAs adjacent to disease-associated SNPs also appears promising for identifying functionally relevant lncRNAs.…”

Section: Discussionmentioning

confidence: 99%

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

Johnson,

Sargsyan,

Neiman

et al. 2024

JCI Insight

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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.

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Section: Discussionmentioning

confidence: 99%