hsa_circ_0001818 regulates the function of macrophages in sepsis by inhibiting miR-17-3p, miR-433-3p, and miR-642a-5p

Sepsis is a leading cause of death due to severe infections. Macrophages are important players in regulating the development of sepsis. Notably, hsa_circ_0001818 is highly expressed in the serum exosomes of sepsis patients and has shown potential as a diagnostic marker for the condition. However, its regulatory role in sepsis remains unclear. Here, we reported that hsa_circ_0001818 expression in macrophages is increased in sepsis. After hsa_circ_0001818 silencing, the apoptotic rate and release of inflammatory cytokines decreased, while phagocytic function of macrophages increased. In contrast, after hsa_circ_0001818 overexpression, the apoptotic rate and the release of inflammatory factors increased, whereas phagocytic function of macrophages decreased. In addition, mechanistic studies and rescue experiments confirmed that hsa_circ_0001818 adsorbs miR-17-3p, miR-433-3p, and miR-642a-5p as sponges, competitively inhibiting the expression of downstream target genes and regulating macrophage function. That is, hsa_circ_0001818 increased the apoptosis rate of macrophages through the miR-17-3p/caspase-3 (CASP3) axis, inhibited the phagocytic function of macrophages by adsorbing miR-433-3p and miR-642a-5p, and increased the secretion level of macrophage inflammatory factors by regulating the zinc finger and BTB domain-containing 20 (ZBTB20)/nuclear factor kappa-B (NF-κB) axis through miR-433-3p and miR-642a-5p. This study revealed the important role of hsa_circ_0001818 in sepsis and provided a new theoretical basis for the precise treatment of sepsis.