In this study, we aim to investigate the role of miR-30a-5p in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) using LPS-induced A549 cells and mice. We found cell viability was significantly declined accompanied by cell apoptosis and cell cycle arrest at G0/G1 phase in LPS-treated A549 cells. MiR-30a-5p was down-regulated by LPS treatment and miR-30a-5p significantly protected A549 cells from LPS-induced injury by increasing cell viability, reducing cell apoptosis, promoting cell cycle progression, and inhibiting inflammatory reactions. Dual-luciferase activity demonstrated that RUNX2 was a direct target for miR-30a-5p and its expression was negatively and directly regulated by miR-30a-5p. Over-expression of RUNX2 weakened the inhibitory effect of miR-30a-5p on inflammatory injury. In vivo, over-expression of miR-30a-5p alleviated LPS-induced inflammatory responses and lung injury in LPS-administrated mice. Besides, miR-30a-5p repressed LPS-elevated phosphorylation levels of the signal transducer and activator of transcription 3 (STAT3) and c-Jun N-terminal kinase (JNK), IκBα degradation, and NF-κB p65 phosphorylation. In conclusion, miR-30a-5p ameliorates LPS-induced inflammatory injury in A549 cells and mice via targeting RUNX2 and related signaling pathways, thereby influencing the progression of ARDS.

在本研究中，我们旨在使用 LPS 诱导的 A549 细胞和小鼠研究 miR-30a-5p 在急性肺损伤/急性呼吸窘迫综合征 (ALI/ARDS) 中的作用。我们发现在 LPS 处理的 A549 细胞中，细胞活力显着下降，伴随着细胞凋亡和 G0/G1 期细胞周期停滞。LPS 处理下调 MiR-30a-5p，miR-30a-5p 通过增加细胞活力、减少细胞凋亡、促进细胞周期进程和抑制炎症反应显着保护 A549 细胞免受 LPS 诱导的损伤。双荧光素酶活性表明 RUNX2 是 miR-30a-5p 的直接靶标，其表达受到 miR-30a-5p 的负向和直接调节。RUNX2的过表达削弱了miR-30a-5p对炎症损伤的抑制作用。体内, miR-30a-5p 的过表达减轻了 LPS 给药小鼠中 LPS 诱导的炎症反应和肺损伤。此外，miR-30a-5p 抑制 LPS 升高的信号转导和转录激活因子 3 (STAT3) 和 c-Jun N-末端激酶 (JNK) 的磷酸化水平、IκBα 降解和 NF-κB p65 磷酸化。总之，miR-30a-5p通过靶向RUNX2和相关信号通路改善LPS诱导的A549细胞和小鼠炎症损伤，从而影响ARDS的进展。