Activation of DNA methyltransferase 3a by Epstein-Barr nuclear antigen 1 in gastric carcinoma

摘要

BackgroundEpstein–Barr nuclear antigen 1 (EBNA1) is expressed in all Epstein–Barr virus (EBV)-infected cells. It interacts with a variety of cellular proteins and activates the transcription of other EBV latency genes, which plays an important role in the persistence of the EBV genome during latent infection.AimSeveral studies have shown that EBV infection induces the expression of DNA methyltransferases (DNMTs) and causes extensive methylation of the whole genome in EBV-associated gastric carcinoma (EBVaGC). However, the specific mechanism by which EBV regulates DNMTs expression is still unclear.Methods and resultsEBNA1 plasmid and siRNA were transfected to evaluate the effect of EBNA1 on DNMT3a expression. Molecular biology experiments were used to detect the biological function of DNMT3a and its effect on EBV latency in gastric carcinoma cells. We showed that EBNA1 upregulated DNMT3a expression through the E2F1 transcription factor (E2F1) in EBVaGC. DNMT3a knockdown restrained cell proliferation, induced cell cycle arrest, promoted cell apoptosis and suppressed cell migration in vitro.ConclusionsOur results showed a new mechanism for EBV to regulate the expression of DNMT3a. Targeting the EBNA1/E2F1/DNMT3a axis may provide an alternative therapeutic strategy in the treatment of EBVaGC with high DNMT3a expression.

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