Long non-coding RNA IL6-AS1 promotes severe community-acquired pneumonia in children through the miR-149-5p/MAPK6
Chang Liu1, Fanghua Jian2, Jing Li3
1Department of Respiratory, The Third Hospital of Shijiazhuang, Shijiazhuang, 050011, China.
Insights
Long non-coding RNA IL6-AS1 (lncRNA IL6-AS1) exacerbates severe community-acquired pneumonia (SCAP) by promoting inflammation and cell damage. This lncRNA plays a crucial role in SCAP pathogenesis via the miR-149-5p/MAPK6 pathway.
Area of Science:
- Molecular Biology
- Pediatric Pulmonology
- Biochemistry
Background:
- Severe community-acquired pneumonia (SCAP) poses a significant threat to children's health.
- Understanding the molecular mechanisms underlying SCAP is critical for developing effective treatments.
Purpose of the Study:
- To investigate the role and regulatory mechanisms of long non-coding RNA IL6-AS1 (lncRNA IL6-AS1) in SCAP.
- To explore the potential diagnostic and prognostic value of lncRNA IL6-AS1 in pediatric SCAP.
Main Methods:
- Comparative analysis of lncRNA IL6-AS1 expression in 160 children with SCAP and 160 healthy controls.
- In vitro modeling of SCAP using lipopolysaccharide (LPS)-induced human embryonic lung fibroblasts (MRC-5).
- Quantitative PCR, CCK-8 assay, flow cytometry, ELISA, RIP, and dual luciferase assays were employed to assess gene expression, cell viability, apoptosis, and molecular interactions.
Main Results:
- lncRNA IL6-AS1 expression was significantly upregulated in children with SCAP and correlated positively with inflammatory markers (CRP, LDH, PCT).
- High lncRNA IL6-AS1 expression was associated with reduced survival rates in SCAP patients, indicating its prognostic value.
- In vitro, lncRNA IL6-AS1 inhibition reduced LPS-induced cell damage, apoptosis, and inflammation.
- A regulatory axis was identified: lncRNA IL6-AS1 targets miR-149-5p, which in turn targets MAPK6, mediating SCAP progression.
Conclusions:
- lncRNA IL6-AS1 aggravates SCAP by promoting inflammatory responses and cell damage.
- The miR-149-5p/MAPK6 axis is a key pathway through which lncRNA IL6-AS1 exerts its detrimental effects in SCAP.
- lncRNA IL6-AS1 serves as a potential diagnostic biomarker and therapeutic target for SCAP.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
IL6-AS1 aggravated SCAP inflammatory response and cell damage through the miR-149-5p/MAPK6 axis.
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