Circular RNAs (circRNAs) have been confirmed to mediate infantile pneumonia development. In this, we investigated the role and new mechanism of circ_0035292 regulating infantile pneumonia progression. Lipopolysaccharide (LPS)-treated WI-38 cells were used to mimic infantile pneumonia cell injury models. Quantitative real-time PCR was used to measure circ_0035292, microRNA (miR)-494-3p and toll-like receptor 4 (TLR4). Cell proliferation and apoptosis were assessed by MTT assay, EdU assay, and flow cytometry. Protein expression was tested using western blot analysis. Inflammation and oxidative stress were evaluated by measuring IL-6, IL-1β, MDA and SOD levels using ELISA assay and corresponding kits. RNA interaction was confirmed by dual-luciferase reporter assay and RIP assay. Circ_0035292 had elevated expression in infantile pneumonia patients and LPS-induced WI-38 cells. Silenced circ_0035292 could enhance WI-38 cell proliferation, while suppress apoptosis, inflammation and oxidative stress under LPS treatment. Mechanically, circ_0035292 targeted miR-494-3p to positively regulate TLR4. The rescue experiments indicated that miR-494-3p inhibitor abolished the function of circ_0035292 knockdown, and TLR4 overexpression reversed the inhibitory effect of miR-494-3p on LPS-induced WI-38 cell injury. Circ_0035292 might be a potential target for infantile pneumonia treatment, which knockdown could relieve LPS-induced cell injury via the regulation of miR-494-3p/TLR4 axis.

Circular RNAs have emerged as important regulators in the pathogenesis of human diseases, including infantile pneumonia (IP). In this study, we aimed to explore the effects of circ_0035292 on lipopolysaccharide (LPS)-treated Wistsar Institute (WI)-38 cells.
Quantitative real-time polymerase chain reaction and western blot were executed to detect the levels of circ_0035292, microRNA-370-3p (miR-370-3p) and transducin β-like 1X related protein 1 (TBL1XR1). Cell counting kit-8, 5-ethynyl-2\'-deoxyuridine, and flow cytometry assessed cell proliferation and apoptosis. Concentrations of inflammatory factors were examined with enzyme linked immunosorbent assay kits. Dual-luciferase reporter assay and RNA immunoprecipitation were adopted to analyze binding between miR-370-3p and circ_0035292 or TBL1XR1.
Circ_0035292 level was increased in IP patients and LPS-triggered WI-38 cells. Circ_0035292 knockdown rescued LPS-mediated WI-38 cell proliferation suppression and WI-38 cell apoptosis and inflammation promotion. Circ_0035292 interacted with miR-370-3p and miR-370-3p directly targeted TBL1XR1. Moreover, miR-370-3p overexpression alleviated LPS-induced WI-38 cell apoptosis and inflammatory injury, which was abrogated via TBL1XR1 upregulation. Circ_0035292 absence inhibited the NF-κB pathway.
Knockdown of circ_0035292 rescued LPS-triggered WI-38 cell injury via miR-370-3p/TBL1XR1 axis and NF-κB pathway.