Exosome-derived miR-BART2-5p and miR-BART11-5p induced epithelial-mesenchymal transition and migration in Epstein-Barr virus-associated gastric carcinoma.

Epstein–Barr virus-associated gastric cancer (EBVaGC) was one of four subtypes of GC and exhibits distinct molecular and clinical characteristics. Exosomes, which serve as important means of intercellular communication in the tumor microenvironment, play a key role in the transmission of the information between tumor cells and the microenvironment. This study aimed to investigate whether EBV-encoded microRNAs (miRNAs) can enter the receptor cells via exosomes and perform their function. Total exosomes were extracted from the culture medium using a total exosome isolation reagent and identified by nanosight tracking analysis, transmission electron microscopy, and Western blotting. Quantitative reverse-transcription polymerase chain reaction detected the expression profiles of EBV-encoded miRNAs in EBV-positive GC cell lines and exosomes. Immunofluorescence techniques were used to detect the uptake of exosomes by the receptor cells. The effects of exosomes derived from different cells and their potential mechanisms were further investigated using Cell-Counting Kit-8, colony formation assay, flow cytometry analysis, transwell assay, and immunofluorescence techniques. The expression profiles of miRNAs in EBV-positive GC cells and exosomes were different. miR-BART2-5p and miR-BART11-5p, which were transmitted to the receptor cells through exosomes, could activate the Wnt/β-catenin pathway and promote migration of receptor cells. EBV may transform the microenvironment into a tumor-promoting environment that induces EBVaGC through exosomes.