The miR-4732-5p/XPR1 axis suppresses the invasion, metastasis, and epithelial–mesenchymal transition of lung adenocarcinoma via the PI3K/Akt/GSK3β/Snail pathway

Abstract

The roles of microRNAs (miRNAs) in the occurrence, metastasis, and prognosis of lung adenocarcinoma (LUAD) have been drawing extensive attention from researchers. The aim of this study is to identify the effects of miR-4732-5p on the migration, invasion, and metastasis of LUAD. In this study, we found that the expression of miR-4732-5p was decreased in LUAD based on the data derived from The Cancer Genome Atlas (TCGA) database, tissues, and cell lines. LUAD patients with a low expression of miR-4732-5p exhibited a lower survival rate. Meanwhile, miR-4732-5p could directly target xenotropic and polytropic retrovirus receptor 1 (XPR1), and elevated XPR1 was observed in LUAD mRNA microarrays, Gene Expression Omnibus (GEO), and The Human Protein Atlas (HPA) database. Overexpression of miR-4732-5p significantly inhibits the migration, invasion, and metastasis of LUAD in vitro and in vivo, which can be reversed by overexpression of XPR1. We also found that the PI3K/Akt/GSK3β/Snail pathway induced by EGF induced EMT could be inhibited by miR-4732-5p overexpression and XPR1 knockdown. The migration and invasion of LUAD could be converted by cytoskeletal rearrangements, and the polymerization of EGF induced F-actin in A549 cells could be inhibited by elevated miR-4732-5p. Our results suggest that miR-4732-5p exerts anti-tumor effects on the invasion and metastasis of LUAD by regulating XPR1 in vivo and in vitro, indicating that the miR-4732-5p/XPR1 axis may be a potential target for LUAD therapeutic intervention.