Sepsis, resulting from a harmful or damaging response to infection, is a complex and severe disease that causes high mortality. Three independent expression profiles of miRNA - GSE94717, GSE149764, and GSE101639 - were collected and integrated to analyze miRNAs associated with sepsis. One miRNA, miR-223-3p, was detected significantly downregulated in patients with sepsis. The upregulated miR-223-3p target genes in patients with sepsis were enriched in central carbon metabolism associated with HIF-1 signaling and galactose metabolism. Specially, three HIF-1 signaling genes - hypoxia-inducible factor 1-alpha (HIF1A), hexokinase 2 (HK2), and MAP kinase-interacting serine/threonine-protein kinase 1 (MKNK1) - were found significantly upregulated in patients with sepsis. Additionally, MKNK1 expression was downregulated in septic responders to early therapeutic treatments. Neutrophils were significantly accumulated in patients with sepsis and decreased in responders after therapy; MKNK1 was significantly positively correlated with neutrophils. Our findings indicate MKNK1, one targets of miR-223-3p, might be involved in sepsis via regulating the neutrophils abundance by mediating the expression inflammation factors.
Keywords: Sepsis; hif-1 signaling; miR-223-3p; mknk1; neutrophils.