Mechanistic study on the regulatory role of hsa-miR-1247-5p and TRIB2 in sepsis-induced acute lung injury

Sepsis is a complex clinical syndrome characterized by an exaggerated systemic inflammatory response to Infection. The lung is the most vulnerable organ in septic patients, leading to acute lung injury (ALI) as a common complication. MicroRNAs (miRNAs) primarily regulate the expression of target genes, influencing disease initiation and progression. This study aimed to evaluate the regulatory role of hsa-miR-1247-5p and TRIB2 in sepsis-induced ALI. Bioinformatics approaches were employed to predict target genes of hsa-miR-1247-5p, followed by validation using a dual-luciferase reporter assay. A lipopolysaccharide (LPS)-induced ALI cell model was established using murine monocyte-macrophage RAW264.7 cells. Techniques including CCK-8, RT-PCR, flow cytometry, mitochondrial membrane potential probe detection, and Western blotting were utilized to investigate the expression and functional roles of hsa-miR-1247-5p and TRIB2 in ALI. The regulatory mechanism was preliminarily assessed by downregulating hsa-miR-1247-5p. The dual-luciferase assay confirmed the direct targeting interaction between hsa-miR-1247-5p and TRIB2. In the sepsis-induced ALI cell model, hsa-miR-1247-5p and TRIB2 exhibited a negative correlation. Suppression of hsa-miR-1247-5p significantly increased cell viability while reducing mRNA levels of inflammatory cytokines, Apoptosis rates, and mitochondrial membrane depolarization. Additionally, downregulation of hsa-miR-1247-5p decreased the expression of pyroptosis-related proteins (Caspase-1, ASC, and GSDMD), thereby inhibiting Pyroptosis. hsa-miR-1247-5p ameliorates sepsis-induced ALI by negatively regulating TRIB2. This study elucidates a potential therapeutic pathway targeting the hsa-miR-1247-5p/TRIB2 axis in ALI management.

Hsa-miR-1247-5p; Lung Injury; Pyroptosis; Sepsis; TRIB2.