Identification of key miRNA‑mRNA pairs in septic mice by bioinformatics analysis

Area of Science:

• Biochemistry
• Genomics
• Immunology

Background:

• Sepsis is a leading cause of death in intensive care units globally.
• The specific microRNAs (miRNAs) and their target genes in sepsis remain largely unidentified.
• Understanding these molecular interactions is crucial for developing effective treatments.

Purpose of the Study:

• To identify key microRNA-mRNA pairs associated with sepsis using integrated bioinformatics analysis.
• To elucidate the potential roles of these pairs in sepsis pathogenesis and immune response.
• To validate identified gene expression changes in a sepsis mouse model.

Main Methods:

• Downloaded and analyzed miRNA and mRNA datasets (GSE74952, GSE55238) from the Gene Expression Omnibus.
• Utilized bioinformatics tools including GEO2R, miRNA target prediction, Gene Ontology, KEGG pathway analysis, and network analysis.
• Validated key gene expression levels using reverse transcription-quantitative PCR in a sepsis mouse model.

Main Results:

• Identified four significant sepsis-related miRNA-mRNA pairs.
• Mmu-miR-370-3p, CD8a, CD247, Zap70, and Ikbkb were identified as key components.
• Enrichment analysis revealed involvement in the T-cell receptor signaling pathway.
• RT-qPCR validated the differential expression of CD8a, CD247, Zap70, and Ikbkb in sepsis models.

Conclusions:

• Successfully identified four novel sepsis-related miRNA-mRNA pairs through comprehensive bioinformatics analysis.
• These identified pairs, particularly those in the T-cell receptor pathway, are implicated in immune regulation during sepsis.
• The findings highlight potential diagnostic biomarkers and therapeutic targets for sepsis management.