MicroRNA-3941 targets IGF2 to control LPS-induced acute pneumonia in A549 cells

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.