Epstein-Barr virus miRNA-BART16 modulates cell proliferation by targeting LMP1.

Epstein-Barr virus (EBV) is a ubiquitous oncogenic herpesvirus associated with various human tumors. Latent membrane protein (LMP) 1 is considered a key oncoprotein in some EBV-associated tumors, while it is absent in EBV-associated gastric carcinoma (EBVaGC). In the present study, we did not detect the mRNA or the protein expression of LMP1 in 10 EBVaGC tissue samples, but we found that miRNA-BART16 was more abundantly expressed in EBVaGC primary tissues than in cell lines. It has been reported that EBV-encoded miRNA-BART16 can target the 3'-untranslated regions of LMP1 and negatively regulate its expression. When a BART16 inhibitor or mimics were transfected into EBVaGC cell lines, both mRNA and protein levels were changed compared with those in controls. We further investigated the role of miRNA-BART16 in EBVaGC. According to the CCK8 assay, the proliferation of GT38 and GT39 cells increased after treatment with a miRNA-BART16 inhibitor. At the same time, the BART16 inhibitor caused increased accumulation of G2/M phase cells by bromodeoxyuridine and propidium iodide staining analysis. In addition, no obvious difference was observed in apoptosis after treatment with an inhibitor or mimics using annexin V staining. Our findings highlight the viral role of EBV-encoded miRNA-BART16 in regulating oncogenic LMP1 expression and a negative association with the proliferation of EBVaGC.