CIRCESPL1 SILENCING PROTECTS AGAINST LPS-INDUCED LUNG FIBROBLAST DYSFUNCTION PARTLY BY TARGETING THE MIR-146B-3P/TRAF1 AXIS IN PNEUMONIA.

Abstract

Background: Neonatal pneumonia is a common disease in the neonatal period with high mortality. The present work concentrated on the role and mechanism of circular RNA extra spindle pole bodies like 1, separase (circESPL1) in LPS-induced dysfunction of lung fibroblasts. Methods: Reverse transcription-quantitative polymerase chain reaction and Western blot assay were conducted to analyze RNA and protein expression, respectively. Cell viability, proliferation, apoptosis, and inflammation were assessed by Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to verify the intermolecular interactions among circESPL1, miR-146b-3p, and TRAF1. Results: CircESPL1 expression was upregulated in the serum samples of pneumonia patients and LPS-induced lung fibroblasts. CircESPL1 silencing protected lung fibroblasts against LPS-induced dysfunction. CircESPL1 bound to microRNA-146b-3p (miR-146b-3p) in lung fibroblasts. CircESPL1 knockdown-mediated protective effects on LPS-induced lung fibroblasts were largely reversed by the silence of miR-146b-3p. miR-146b-3p directly interacted with the 3' untranslated region of TNF receptor associated factor 1 (TRAF1), and TRAF1 expression was regulated by the circESPL1/miR-146b-3p axis in lung fibroblasts. TRAF1 overexpression largely reversed miR-146b-3p accumulation-mediated protective effects on LPS-induced lung fibroblasts. Conclusion: CircESPL1 knockdown protected lung fibroblasts from LPS-induced injury partly by targeting the miR-146b-3p/TRAF1 axis.