The Epstein–Barr Virus Envelope Glycoprotein BALF4 Promotes the Ubiquitination and Degradation of RNA Acetyltransferase NAT10 Suppressing Gastric Cancer Progression

ABSTRACT Epstein–Barr virus‐associated gastric cancer (EBVaGC) is a unique subtype of gastric cancer (GC) with distinct molecular characteristics that generally has a better prognosis. Bam HI‐A leftward frame 4 ( BALF4 ), an envelope glycoprotein encoded by the Epstein‐Barr virus (EBV), plays an important role in EBV infection. However, its biological function and potential molecular mechanisms in EBVaGC remain unclear. This study aimed to investigate the impact of the highly expressed viral gene BALF4 on the progression of EBVaGC. Here, we detected the expression of BALF4 in GC tissue chips and validated that the presence of BALF4 might be associated with a favorable prognosis in EBVaGC. The results showed that BALF4 inhibited the proliferation, migration, and invasion of GC cells in vitro and in vivo. In addition, we discovered that BALF4 interacts with N‐acetyltransferase 10 (NAT10). High expression of NAT10 in GC tissues promotes the malignant phenotype of GC cells. We discovered that BALF4 could inhibit the malignant progression of GC by promoting the ubiquitination and degradation of NAT10. In summary, our study revealed a possible mechanism explaining the favorable prognosis of the EBVaGC subtype, which contributes to a better understanding of this special type of GC.