Knockdown of the IncRNA MALA T1 alleviates lipopolysaccharide-induced A549 cell injury by targeting the miR-17-5p/FOXA1 axis

Abstract

Long-noncoding RNA s (IncRNAs) are crucial for the pathophysiology of acute lung injury (ALI). Metastasis-associated lung adenocarcinoma transcript 1 (MALA T1) suppresses inflammatory responses via microRNA (miR)-146a in lipopolysaccharide (LPS)-induced ALI. However, the molecular mechanisms Underlying the MALA T1-mediated regulation of cell proliferation and apoptosis in LPS-induced ALI remain unclear. In the present study, it was foUnd that LPS treatment upregulated MALA T1 expression and suppressed the proliferation of A549 cells. MALA T1 knockdown significantly promoted the proliferation and G1/S phase transition and inhibited apoptosis in LPS-treated A549 cells. In addition, miR-17-5p was a direct target of MALA T1. miR-17-5p expression was downregulated and FOXA1 expression was upregulated in LPS-treated A549 cells. Further, MALA T1 knockdown promoted miR-17-5p expression and inhibited FOXA1 expression, whereas the combined suppression of MALA T1 and miR-17-5p induced FOXA1 expression. Moreover, miR-17-5p knockdown reversed the effects of MALA T1 suppression on LPS-induced A549 cell proliferation. These results indicated that MALA T1 serves as a competing endogenous IncRNA that, by sequestering miR-17-5p, stimulates FOXA1 expression and mediates LPS-induced A549 cell injury. In conclusion, the present study demonstrated that MALA T1 knockdown alleviates LPS-induced A549 cell injury by targeting the miR-17-5p/FOXA1 axis.