{Reference Type}: Journal Article
{Title}: Circular RNA circESPL1 knockdown alleviates lipopolysaccharide (LPS)-induced lung cell injury via sponging miR-326 to regulate MAPK14.
{Author}: Liang Y;Miao Y;Xiang J;
{Journal}: Int Immunopharmacol
{Volume}: 112
{Issue}: 0
{Year}: Aug 2022 26
{Factor}: 5.714
{DOI}: 10.1016/j.intimp.2022.109146
{Abstract}: <B>BACKGROUND: </B>Infantile pneumonia (IP) is a common inflammatory disease, which brings a heavy burden to young children's health. Previous studies suggested that circular RNA (circRNA) hsa_circ_0026579 (also called circESPL1) was significantly upregulated in pneumonia patients, which was associated with the disease severity. This subject aimed to explore the functional effects and potential regulatory mechanism of circESPL1 on lipopolysaccharide (LPS)-induced lung cell injury.<BR><B>METHODS: </B>WI-38 and MRC-5 cells were stimulated by LPS to mimic the inflammatory injury model. CircESPL1, microRNA-326 (miR-326), and Mitogen-Activated Protein Kinase 14 (MAPK14)levels were measured using real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays were performed to assess cell proliferation and apoptosis. Western blot analysis of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), C-caspase 3, and MAPK14 protein levels. Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and IL-1β levels were examined using an Enzyme-linked immunosorbent assay (ELISA). Using Starbase analysis, the binding between miR-326 and circESPL1 or MAPK14 was predicted, followed by confirmation using a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays.<BR><B>RESULTS: </B>Increased circESPL1 and MAPK14, and reduced miR-326 were observed in serum samples from preeclampsia sufferers and LPS-treated lung cells (P < 0.05). Furthermore, circESPL1 deficiency overturned LPS-mediated cell proliferation, apoptosis, and inflammatory response in vitro (P < 0.05). In terms of molecular mechanisms, circESPL1 worked as a sponge of miR-326, and miR-326 absence reversed the protective role of circESPL1 silencing on LPS-triggered lung cell injury (P < 0.05). Also, miR-326 directly targeted MAPK14, and MAPK14 overexpression abolished miR-326-mediated impacts under LPS treatment (P < 0.05).<BR><B>CONCLUSIONS: </B>CircESPL1 knockdown might attenuate LPS-caused lung cell injury by regulating the miR-326/ MAPK14 axis, providing useful insight for exploring a novel therapeutic approach for IP.