CIRC_0012535 CONTRIBUTES TO LIPOPOLYSACCHARIDE-INDUCED FETAL LUNG FIBROBLAST APOPTOSIS AND INFLAMMATION TO REGULATE INFANTILE PNEUMONIA DEVELOPMENT BY MODULATING THE MIR-338-3P/IL6R SIGNALING.

Background: Infantile pneumonia is a respiratory infection disease, seriously threatening the life of neonatal patients. Circular RNA (circRNA) dysregulation is reported to be involved in pneumonia pathogenesis. Circ_0012535 was previously displayed to be upregulated in blood samples of patients with community-acquired pneumonia. However, circ_0012535's role in this disorder remains unclear. We thus aim to unveil the functions of circ_0012535 in infantile pneumonia. Methods: Fetal lung fibroblasts (WI38) treated with LPS were used as pneumonia cell models. Expression analysis for circ_0012535, miR-338-3p and IL6R was performed using quantitative real-time polymerase chain reaction. Cell counting kit 88), 5-ethynyl-2'-deoxyuridine, and flow cytometry assays were implemented for cell function detection. The release of inflammatory factors, and superoxide dismutase activity and malonaldehyde content were ascertained using commercial kits. The putative binding between miR-338-3p and circ_0012535 or IL6R was validated by dual-luciferase analysis, RIP analysis, and pull-down analysis. Results: Circ_0012535 was highly expressed in LPS-treated WI38 cells. Knockdown of circ_0012535 recovered LPS-inhibited cell viability and proliferation and attenuated LPS-induced cell apoptosis, cell cycle arrest, inflammation, and oxidative stress. Circ_0012535 bound to miR-338-3p and negatively regulated miR-338-3p expression. Inhibition of miR-338-3p reversed the role of circ_0012535 knockdown, thereby recovering LPS-induced WI38 cell apoptosis and inflammation. MiR-338-3p bound to IL6R 3'UTR, and circ_0012535 shared miR-338-3p binding site with IL6R. IL6R overexpression reversed the role of miR-338-3p, thereby recovering LPS-induced WI38 cell apoptosis and inflammation. Conclusion: Circ_0012535 supported LPS-induced WI38 cell apoptosis and inflammation to promote the progression of infantile pneumonia, and circ_0012535 functioned partly by targeting the miR-338-3p/IL6R signaling.