MiR-297 alleviates LPS-induced A549 cell and mice lung injury via targeting cyclin dependent kinase 8.

In recent decades, microRNAs (miRNAs) have been reported to play an important role in the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To explore the underlying mechanisms of miR-297 in ALI/ARDS, we investigated its role in lipopolysaccharide (LPS)-induced A549 cell and mice lung injury model. We found that the expression of miR-297 decreased in LPS-induced A549 cells or serum of ALI/ARDS mice. Moreover, LPS suppressed A549 cell viability, promoted apoptosis and increased the expressions of inflammatory and autophagy-related factors. Conversely, overexpression of miR-297 increased cell proliferation and reduced cell apoptosis, and alleviated inflammatory cytokines secretion and autophagy in the presence of LPS. Importantly, miR-297 directly inhibited transcription of cyclin dependent kinase 8 (CDK8) by binding to the 3'-untranslated region (3'-UTR) of CDK8 mRNA, and the expression of CDK8 was negatively regulated by miR-297. Silencing of CDK8 promoted the anti-inflammatory and anti-apoptotic effects of miR-297 in LPS-mediated A549 cells. The expressions of phosphorylated p65 (p-p65)/p65 and phosphorylated inhibitor kappa B-α (p-IκBα)/IκBα were dramatically decreased by miR-297 mimics and silencing of CDK8. In vivo, miR-297 alleviated LPS-induced inflammatory responses and lung injury in ALI/ARDS mice. In conclusion, our findings suggested that miR-297 affects nuclear factor-kappa B (NF-κB) pathway to alleviate LPS-induced A549 cell and mice lung injury via targeting CDK8 expression.

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