Identification and validation of key biomarkers based on RNA methylation genes in sepsis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 28, 2023

RNA methylation is closely involved in immune regulation, but its role sepsis remains unknown. Here, we aim to investigate the of methylation-associated genes (RMGs) classifying and diagnosing sepsis.Five types RMGs (m1A, m5C, m6Am, m7G Ψ) were used identify subgroups based on gene expression profile data obtained from GEO database (GSE57065, GSE65682, GSE95233). Unsupervised clustering analysis was distinct modification subtypes. The CIBERSORT, WGCNA, GO KEGG performed explore infiltration pattern biological function each cluster. RF, SVM, XGB, GLM algorithm applied diagnostic sepsis. Finally, levels five key verified by collecting PBMCs septic patients using qRT-PCR, their efficacy for combination with clinical ROC analysis.Sepsis divided into three subtypes (cluster 1 3). Cluster highly expressed NSUN7 TRMT6, characteristic neutrophil activation upregulation MAPK signaling pathways. 2 NSUN3, featured regulation mRNA stability amino acid metabolism. NSUN5 NSUN6 upregulated cluster 3 which ribonucleoprotein complex biogenesis carbohydrate metabolism In addition, identified that (NSUN7, NOP2, PUS1, PUS3 FTO) could as biomarkers clinic diagnose For validation, determined relative expressions NSUN7, PUS1 upregulated, while FTO downregulated patients. area under curve (AUC) 0.828, 0.707, 0.846, 0.834 0.976, respectively.Our study uncovered dysregulation pathogenesis sepsis, providing new insights classification endotypes. We also revealed hub novel potential targets treatment.

Language: Английский

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N-acetyltransferase 10 regulates alphavirus replication via N4-acetylcytidine (ac4C) modification of the lymphocyte antigen six family member E (LY6E) mRNA

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(1)

Published: Jan. 3, 2024

ABSTRACT Epitranscriptomic RNA modifications can regulate the stability of mRNA and affect cellular viral functions. The N4-acetylcytidine (ac4C) modification in genome was recently found to promote replication; however, mechanism by which acetylation host regulates replication remains unclear. To help elucidate this mechanism, roles N-acetyltransferase 10 (NAT10) ac4C during infection processes alphavirus, Sindbis virus (SINV), were investigated. Cellular NAT10 upregulated, promoted after alphavirus infection, while loss or inhibition its activity reduced replication. enhanced as it helped maintain lymphocyte antigen six family member E mRNA, is a multifunctional interferon-stimulated gene that promotes thus have non-conventional role life cycle through regulating instead could be potential target development new antivirals. IMPORTANCE not yet fully understood. In study, regulation prototype SINV results increased levels increases level RNA. positively an activity-dependent manner. Mechanistically, modifies (LY6E) mRNA—the site within 3′-untranslated region (UTR) LY6E essential for translation stability. findings study demonstrate regulated efficiency only 5′-UTR coding sequence but also via 3′-UTR region. impacting identified, indicating when developing

Language: Английский

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Ficolin-A/2 Aggravates Severe Lung Injury through Neutrophil Extracellular Traps Mediated by Gasdermin D–Induced Pyroptosis

American Journal Of Pathology, Journal Year: 2024, Volume and Issue: 194(6), P. 989 - 1006

Published: March 3, 2024

Language: Английский

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Acetyl-CoA-dependent ac4C acetylation promotes the osteogenic differentiation of LPS-stimulated BMSCs

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 133, P. 112124 - 112124

Published: April 24, 2024

Language: Английский

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NAT10 and cytidine acetylation in mRNA: intersecting paths in development and disease

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 87, P. 102207 - 102207

Published: May 30, 2024

Language: Английский

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