MiR-6747-5p suppresses angiogenesis in esophageal squamous cell carcinoma by targeting EGFL6

Epidermal growth factor-like domain 6 (EGFL6) plays a crucial role in angiogenesis in various malignant tumors. This study aimed to screen microRNAs (miRNAs) targeting EGFL6 and explore their mechanisms in regulating angiogenesis in esophageal squamous cell carcinoma (ESCC) cells. After analyzing the miRNA expression profiles of ESCC and using the target prediction algorithm, we screened three miRNAs that could potentially target EGFL6. By dual luciferase reporter gene assay and western blot, we found that miR-6747-5p could directly target EGFL6 and down-regulate EGFL6 expression in ESCC cells. The results of clone formation, CCK-8, Transwell, wound healing, and endothelial cell tube formation assay showed that miR-6747-5p exerted a significant inhibitory effect on the proliferation, migration, invasion, and angiogenesis of ESCC cells. At the same time, we observed that the phosphorylation levels of AKT and MAPK were decreased, the epithelial-mesenchymal transition (EMT) related E-cadherin expression was downregulated while N-cadherin was upregulated, and the protein expression of the pro-angiogenic factors, including platelet-derived growth factor subunit B (PDGFB), fibroblast growth factor 2 (FGF2), and angiogenin (ANG) were inhibited transfected with miR-6747-5p mimics. Further studies showed that the overexpression vectors of EGFL6 transfected into ESCC cells could reverse the inhibitory effects induced by miR-6747-5p. These findings reveal that miR-6747-5p could target EGFL6 and inhibit tumor angiogenesis and ESCC progression. miR-6747-5p may be a promising biomarker for the anti-angiogenic treatment of ESCC.