Epstein-Barr virus miR-BART4-3p regulates cell proliferation, apoptosis, and migration by targeting AXL in gastric carcinoma

Abstract

To investigate the role of miR-BART4-3p in EBV-associated gastric cancer (EBVaGC) and its regulation of cell proliferation, apoptosis, and migration by targeting AXL in GC. Quantitative real-time PCR and western blot were used to detect the expression of AXL. The methylation status of AXL gene promoter region was determined by bisulfite sequencing PCR. Luciferase reporter assay was used to detect whether miR-BART4-3p targets AXL. The key molecules of EMT and PI3K/AKT pathway were used to examine by western blot. CCK8, Transwell, and flow cytometry were used to detect the phenotypic gastric cancer cells after interference with AXL and miR-BART4-3p. EBV infection inhibited the expression of AXL in GC cells and the inhibition was not caused by the change of promoter methylation status. MiR-BART4-3p directly targeted AXL. Moreover, both inhibition of miR-BART4-3p and AXL inhibited cell proliferation and migration and promoted cell apoptosis. In addition, E-cadherin, Vimentin, ZEB1, and p-AKT were found to be the downstream molecules of the miR-BART4-3p/AXL pathway. The change of promoter methylation status was not the reason for the downregulation of AXL expression in EBV-positive cells. MiR-BART4-3p may inhibit the proliferation and migration and promote apoptosis of GC cells by directly targeting AXL.

Keywords: AXL; EBV; Gastric cancer; MicroRNA.