| First Author | Xi X | Year | 2020 |
| Journal | Int Immunopharmacol | Volume | 80 |
| Pages | 106197 | PubMed ID | 31945608 |
| Mgi Jnum | J:298406 | Mgi Id | MGI:6480083 |
| Doi | 10.1016/j.intimp.2020.106197 | Citation | Xi X, et al. (2020) MiR-297 alleviates LPS-induced A549 cell and mice lung injury via targeting cyclin dependent kinase 8. Int Immunopharmacol 80:106197 |
| abstractText | 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-alpha (p-IkappaBalpha)/IkappaBalpha 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-kappaB) pathway to alleviate LPS-induced A549 cell and mice lung injury via targeting CDK8 expression. |
