Identification of oxygenation impairment–associated gene networks in ARDS through integrated mRNA and miRNA analysis

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with high mortality and complex pathophysiology, yet molecularly targeted therapies remain undeveloped. In particular, the microRNA (miRNA)-mRNA regulatory network underlying ARDS is poorly understood. This study aimed to elucidate the miRNA-mRNA interactions associated with the pathophysiology of ARDS. METHODS: mRNA-Seq and miRNA-Seq were performed in 34 patients with ARDS and healthy controls. Gene and miRNA co-expression modules were constructed using Weighted Gene Co-expression Network Analysis. miRNA-mRNA regulatory relationships were inferred through an integrated analysis of predicted and experimentally validated miRNA targets. Molecular signatures were quantified via single-sample gene set enrichment analysis, and module structure preservation was evaluated in an external pneumonia cohort. RESULTS: A key mRNA co-expression module was identified that exhibited the strongest negative correlation with the P/F ratio, along with a negatively correlated miRNA co-expression module. The miRNA module, centered on miR-361-5p and miR-186-5p, formed a regulatory network broadly controlling gene clusters involved in ubiquitin ligase activity and cellular stress response pathways. This network demonstrated a strong association with the P/F ratio and showed high structural preservation in the external pneumonia cohort. CONCLUSION: A miRNA-mRNA regulatory network linked to impaired oxygenation in patients with ARDS has been identified. The network highlights miRNAs as potential key regulators of disease progression and suggests their utility as biomarkers of disease severity and prospective therapeutic targets.