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Published on: March 21, 2021
microRNA‑3941 targets IGF2 to control LPS‑induced acute pneumonia in A549 cells
Shinuan Fei1, Lichun Cao2, Liangzhi Pan3
1Department of Pediatrics, Edong Healthcare Group, Huangshi Maternity and Children's Health Hospital, Huangshi, Hubei 435000, P.R. China.
Abstract:
The present study aimed to investigate the potential roles and regulatory mechanism of microRNA (miR)-3941 in lipopolysaccharides (LPS)‑induced acute pneumonia. The expression of miR‑3941 in child patients with acute pneumonia was detected and A549 cells were treated with LPS to establish the cellular model of acute pneumonia. The effects of miR‑3941 in LPS‑induced cell injury were investigated by assessing cell viability, apoptosis and inflammation. In addition, the regulatory relationship between miR‑3941 and insulin‑like growth factor 2 (IGF2) was explored, as well as the association between miR‑3941 and the phosphatidylinositol‑4,5‑bisphosphate 3‑kinase/protein kinase B (PI3K/AKT) pathway. miR‑3941 was significantly down‑regulated in patients with acute pneumonia (P<0.01). In the cell model of acute pneumonia, LPS treatment significantly induced cell injury via inhibiting cell viability (P<0.05 or P<0.01), inducing cell apoptosis (P<0.01) and enhancing the production of cytokines [interleukin (IL)‑6, IL‑8 and tumor necrosis factor‑α; P<0.01 or P<0.001]. LPS treatment also resulted in a significantly decreased expression of miR‑3941 in A549 cells (P<0.01) and the overexpression of miR‑3941 significantly alleviated LPS‑induced cell injury (P<0.05). In addition, IGF2 was confirmed as a direct target gene of miR‑3941. Knockdown of IGF2 significantly alleviated LPS‑induced cell injury (P<0.05, P<0.01 or P<0.001), which was significantly reversed by suppression of miR‑3941 (P<0.05, P<0.01 or P<0.001). Furthermore, inhibition of miR‑3941 was demonstrated to activate the PI3K/AKT pathway, which was inhibited following knockdown of IGF2. The present study indicates that miR‑3941 is downregulated in child patients with acute pneumonia and that downregulation of miR‑3941 may promote LPS‑induced cell injury in A549 cells via targeting IGF2 to regulate the activation of the PI3K/AKT pathway. Therefore, miR‑3941 may be a potential therapeutic target for the treatment of acute pneumonia in child patients.
Insights
MicroRNA-3941 (miR-3941) is downregulated in childhood acute pneumonia, exacerbating lung injury by targeting insulin-like growth factor 2 (IGF2) and activating the PI3K/AKT pathway. Restoring miR-3941 shows therapeutic potential.
Area of Science:
- Molecular Biology
- Immunology
- Pulmonology
Background:
- Acute pneumonia is a significant cause of childhood morbidity.
- Lipopolysaccharides (LPS) trigger inflammatory responses implicated in pneumonia pathogenesis.
- MicroRNAs (miRNAs) play crucial roles in regulating cellular processes and disease development.
Purpose of the Study:
- To investigate the role and regulatory mechanism of microRNA-3941 (miR-3941) in lipopolysaccharides (LPS)-induced acute pneumonia.
- To explore the relationship between miR-3941, insulin-like growth factor 2 (IGF2), and the PI3K/AKT pathway in acute pneumonia.
Main Methods:
- Detected miR-3941 expression in child patients with acute pneumonia.
- Established a cellular model of acute pneumonia using LPS-treated A549 cells.
- Assessed cell viability, apoptosis, inflammation, and the expression of miR-3941, IGF2, and PI3K/AKT pathway components.
Main Results:
- miR-3941 was significantly downregulated in patients and LPS-treated cells.
- LPS induced cell injury, apoptosis, and inflammation, accompanied by decreased miR-3941.
- Overexpression of miR-3941 alleviated LPS-induced injury; IGF2 was identified as a direct target, and its knockdown mimicked miR-3941's protective effects.
- miR-3941 inhibited PI3K/AKT pathway activation, while IGF2 knockdown reversed this inhibition.
Conclusions:
- Downregulation of miR-3941 contributes to LPS-induced acute pneumonia by targeting IGF2 and activating the PI3K/AKT pathway.
- miR-3941 demonstrates potential as a therapeutic target for acute pneumonia in children.
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