Abstract
Background Long non-coding RNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) plays an important role in the pathophysiological process of inflammation. We aimed to investigate MALAT1 and its function in modulating miRNA-181a-3p and Bcl-2 in lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods We analysed MALAT1 in ALI patients, as well as the alveolar epithelial cell models of LPS-induced injury. The expression of MALAT1 and miRNA-181a-3p were evaluated by qRT-PCR, and Bcl-2 was measured by western blot. Inflammatory factors tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 mRNA levels were also quantified by qRT-PCR. Luciferase reporter assay was used to verify direct interaction between MALAT1 and miRNA-181a-3p, or miRNA-181a-3p and Bcl-2. Transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) assay was performed to detect alveolar epithelial cell apoptosis. Results Serum MALAT1 and Bcl-2 levels decreased in ALI patients, whereas miRNA-181a-3p, TNF-α, IL-1β and IL-6 levels increased (P<0.01). MALAT1 was inversely correlated to miRNA-181a-3p (R=-0.508, P=0.0031) in ALI patients. SiMALAT1 transfection upregulated miRNA-181a-3p level and downregulated Bcl-2 expression, aggravating alveolar epithelial cell apoptosis. MiRNA-181a-3p downregulated the Bcl-2 expression both in LPS-induced ALI rats and alveolar epithelial cells, as well as promoted apoptosis. TNF-α, IL-1β and IL-6 levels increased after LPS stimulation and siMALAT1 transfection. Conclusions The results demonstrate that LPS-induced ALI decreases lncRNA MALAT1, increases miRNA-181a-3p and inflammatory factor expression, downregulates the Bcl-2 level and promotes alveolar epithelial cell apoptosis. Down-regulation of MALAT1 may erase the protection of alveolar epithelial cells from LPS-induced ALI via up-regulating of miRNA-181a-3p.
miR-24-p53 pathway evoked by oxidative stress promotes lens epithelial cell apoptosis in age-related cataracts
