Whole-Transcriptome Profiling Reveals RNA Expression Dynamics and ceRNA Network Remodeling across Health, Sepsis, and Sepsis-Associated Acute Respiratory Distress Syndrome [RNA-Seq]

Background: Sepsis-associated acute respiratory distress syndrome (ARDS) is a severe manifestation of infection-related organ dysfunction characterized by dysregulated immune-inflammatory responses and disruption of tissue barriers. However, the whole-transcriptome alterations underlying the progression from sepsis to sepsis-associated ARDS remain insufficiently characterized. Therefore, this study aimed to systematically characterize the expression patterns of mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) in peripheral blood from healthy controls, sepsis without ARDS, and sepsis-associated ARDS patients.Methods: 12 participants were enrolled, comprising four healthy controls (HC group), 4 patients with sepsis without ARDS (SWA group), and 4 patients with sepsis-associated ARDS (SA group). Peripheral blood samples were obtained and subjected to whole-transcriptome sequencing. Trend analysis was performed to identify transcripts exhibiting monotonic increases or decreases across the HC–SWA–SA sequence. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were subsequently performed. Target-gene prediction and expression-correlation analyses were also performed to construct a competing endogenous RNA (ceRNA) regulatory network.Results: All sequencing datasets passed the quality control and were suitable for the following analyses. A total of 773 trend genes were identified, of which 350 were progressively upregulated and 423 were progressively downregulated. These genes were predominantly enriched in immune responses, cell adhesion, cytokine production, extracellular matrix-related processes, MAPK and PI3K–Akt signaling pathways, integrin signaling, focal adhesion, ECM–receptor interaction, and antigen processing and presentation. A total of 189 trend lncRNAs, 252 trend circRNAs, and six trend miRNAs were identified. Their predicted functions were associated with RNA metabolism, translational regulation, chromatin-associated regulation, cytoskeletal organization, epithelial barrier integrity, cell polarity, and intracellular trafficking. The resulting ceRNA network contained several miRNA-centered modules involving hsa-miR-193b-3p, hsa-let-7b-3p, hsa-miR-223-3p, hsa-miR-223-5p, novel_mir_76, and novel_mir_177. These modules were functionally associated mainly with ion transport, calcium signaling, membrane-channel activity, tight-junction regulation, and vesicular trafficking. Conclusion: This study delineates an integrated whole-transcriptome landscape of progressive RNA expression alterations across the transition from health to sepsis without ARDS and, ultimately, to sepsis-associated ARDS. The findings suggest that coordinated dysregulation of coding and non-coding RNAs may contribute to immune-inflammatory activation, extracellular matrix remodeling, barrier dysfunction, and altered post-transcriptional regulation. Collectively, these findings highlight candidate molecular signatures and regulatory axes that warrant further investigation in mechanistic and biomarker-oriented studies of sepsis-associated ARDS.