miR-320a-3P alleviates the epithelial-mesenchymal transition of A549 cells by activation of STAT3/SMAD3 signaling in a pulmonary fibrosis model

Abstract

Pulmonary fibrosis (PF) is a common, chronic and incurable lung disease, in which the lungs become scarred over time. MicroRNAs (miRNAs/miRs) serve key roles in various biological processes, including cell proliferation, differentiation, apoptosis and the regulation of epithelial-mesenchymal transition (EMT) process. The aim of the present study was to investigate the underlying mechanism of miR-320a-3p as a potential therapeutic target for PF. Clinical samples and microarray datasets collected from various databases were used to evaluate the expression of miR-320a-3p in PF. A549 cells were used to construct an EMT model of PF. A dual-luciferase reporter assay system was used to identify target genes of miR-320a-3p. Western blot analysis and immunofluorescence staining were used to determine the roles of miR-320a-3p and its target genes in the EMT process in PF. The present study found that, compared with lung tissue of healthy control subjects, the expression of miR-320a-3p in lung tissue of PF patients was significantly reduced. The expression levels of miR-320a-3p decreased in TGF-β1-stimulated A549 cells in a time- and concentration-dependent manner. The overexpression of miR-320a-3p suppressed EMT markers induced by TGF-β1 in A549 cells and STAT3 was identified as a potential target gene of miR-320a-3p. Furthermore, the expression changes of miR-320a-3p and STAT3 were found to significantly affect the expression of phosphorylated SMAD3 in TGF-β1-stimulated A549 cells. Briefly, overexpression of miR-320a-3p could inhibit the EMT process in PF by downregulating STAT3 expression. The mechanism mediating these effects may partly involve crosstalk between the SMAD3 and STAT3.