Long non-coding RNA NEAT1 promotes lipopolysaccharide-induced acute lung injury by regulating miR-424-5p/MAPK14 axis.

BACKGROUND

Many long non-coding RNAs (lncRNAs) have been suggested to play critical roles in acute lung injury (ALI) pathogenesis, including lncRNA nuclear enriched abundant transcript 1 (NEAT1).

OBJECTIVE

We aimed to further elucidate the functions and molecular mechanism of NEAT1 in ALI.

METHODS

Human pulmonary alveolar epithelial cells (HPAEpiCs) stimulated by lipopolysaccharide (LPS) were served as a cellular model of ALI. Cell viability and cell apoptosis were determined by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The expression of NEAT1, microRNA-424-5p (miR-424-5p), and mitogen-activated protein kinase 14 (MAPK14) was measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot analysis. Caspase activity was determined by caspase activity kit. The inflammatory responses were evaluated using enzyme-linked immunosorbent assay (ELISA). The oxidative stress factors were analyzed by corresponding kits.

RESULTS

NEAT1 was upregulated in LPS-stimulated HPAEpiCs. NEAT1 knockdown weakened LPS-induced injury by inhibiting apoptosis, inflammation and oxidative stress in HPAEpiCs. Moreover, miR-424-5p was a direct target of NEAT1, and its knockdown reversed the effects caused by NEAT1 knockdown in LPS-induced HPAEpiCs. Furthermore, MAPK14 was a downstream target of miR-424-5p, and its overexpression attenuated the effects of miR-424-5p on reduction of LPS-induced injury in HPAEpiCs. Besides, NEAT1 acted as a sponge of miR-424-5p to regulate MAPK14 expression.

CONCLUSION

NEAT1 knockdown alleviated LPS-induced injury of HPAEpiCs by regulating miR-424-5p/MAPK14 axis, which provided a potential therapeutic target for the treatment of ALI.