Long non-coding RNA IL6-AS1 promotes severe community-acquired pneumonia in children through the miR-149-5p/MAPK6 axis

Severe community-acquired pneumonia (SCAP) seriously endangers children’s lives. This study aimed to explore the potential regulatory mechanisms of long non-coding RNA IL6-AS1 (lncRNA IL6-AS1) in SCAP.

This study included 160 children with SCAP and 160 healthy controls. Lipopolysaccharide (LPS) was used to induce human embryonic lung fibroblasts (MRC-5) to construct an SCAP cell model. Functional experiments were conducted by combining real-time quantitative PCR, the cell counting kit-8 (CCK-8) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). The targeted regulatory relationship between different genes was verified through RNA immunoprecipitation (RIP) experiment and dual luciferase assay.

In children with SCAP, IL6-AS1 expression showed significant upregulation. IL6-AS1 has a strong diagnostic value for SCAP, and its expression was significantly positively correlated with indicators of inflammatory response intensity (C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin levels (PCT)) in affected children. It may emerge as an independent risk factor influencing the prognosis of SCAP patients, with significantly reduced cumulative survival rates observed in children exhibiting high IL6-AS1 expression. In vitro experimental results showed that IL6-AS1 could be dose-dependently up-regulated by LPS. Inhibiting IL6-AS1 expression could effectively alleviate the decrease in cell activity and increase in apoptosis levels induced by LPS, thereby reducing cell damage and inflammation imbalance. Moreover, IL6-AS1 targeted microRNA-149-5p (miR-149-5p), while miR-149-5p targeted mitogen-activated protein kinase 6 (MAPK6). Further experiments confirmed that concurrent inhibition of miR-149-5p alongside suppression of IL6-AS1 reversed the protective effects mediated by the former. Conversely, simultaneous knockdown of MAPK6 mitigated the cellular damage and inflammatory response induced by miR-149-5p inhibition.

IL6-AS1 aggravated SCAP inflammatory response and cell damage through the miR-149-5p/MAPK6 axis.