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Highlights • The relative expression of miR-BART16 is higher in EBVaGC tissues than cell lines. • Overexpression of miR-BART16 could reduce the LMP1 mRNA and protein levels. • Inhibition the endogenous miR-BART16 increases the LMP1 mRNA and protein level. • BART16 has a vital role on cell proliferation in EBV-associated gastric carcinoma. Abstract 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. [ABSTRACT FROM AUTHOR]

• LMP1 and LMP2A inhibit the expression of COX-2 in EBVaGC. • TRAF2 is involved in the inhibitory effect of LMP1/2A on COX-2. • LMP1 also down-regulates COX-2 by reducing phosphorylation of ERK. Epstein-Barr virus-associated gastric cancer (EBVaGC) accounts for nearly 10% of gastric cancer. Cyclooxygenase-2 (COX-2) plays a crucial role in cancer progression. However, there is no experimental study on the regulation mechanism of EBV on COX-2 in EBVaGC. To understand more about the tumorigenic mechanism of EBVaGC, the study investigated the role of EBV encode latent membrane protein LMP1 and LMP2A in the regulation of COX-2. The expression of COX-2 was examined in EBVaGC and EBV negative gastric cancer (EBVnGC) cell lines. The plasmids were transfected in SGC7901 to overexpress LMP1/2A. Small interfering RNA (si-RNA) targeting LMP1/2A in GT38 and targeting TRAF2 in SGC7901 were used to detect the expression of COX-2. Furthermore, si-ERK1/2 and the MEK inhibitor PD0325901 were used to investigate whether p-ERK participate in the regulation of COX-2 in SGC7901. The overexpression of LMP1 or LMP2A in SGC7901 down-regulates both COX-2 and TRAF2 expression, and knockdown of LMP1 or LMP2A in GT38 resulted in a certain recovery of COX-2 and TRAF2 expression. Moreover, si-TRAF2 indicated that a sharp down-regulation of COX-2. And the decrease of p-ERK also mediates the inhibitory effect of LMP1 on COX-2. In summary, overexpression of LMP1 and LMP2A inhibits COX-2, which is mediated by a decrease of TRAF2, and p-ERK is involved in the inhibition of COX-2 by LMP1 in gastric cancer. [ABSTRACT FROM AUTHOR]