Transcriptome Sequencing of LMP2A-transfected Gastric Cancer Cells Identifies Potential Biomarkers in EBV-associated Gastric Cancer

Epstein-barr virus (EBV) is a well-known human oncogenic virus. However, its molecular mechanisms in the initiation and development of EBV-associated gastric cancer (EBVaGC) remain poorly understood. Latent membrane protein 2A (LMP2A) is an EBV latency-associated protein expressed in part of EBVaGC cases. This study analyzed the effect of LMP2A on the gene expression of gastric cancer cells by transcriptome sequencing on the gastric cancer cell line SGC7901 that expresses LMP2A. The study monitored a total of 238 genes with significant differences in expression, including 101 upregulated genes and 137 downregulated genes. Using the KEGG pathway analysis, it was found that more genes were enriched in the Steroid biosynthesis, Axon guidance, and Terpenoid backbone biosynthesis pathway, and there were 5 genes each enriched in PI3K-Akt and AMPK signaling pathway, all of which were significant. This indicates that LMP2A may be involved in cell biosynthesis, and affects downstream genes and cell biological behavior through AKT and AMPK signaling pathway. Further evaluation confirmed that LMP2A induces ETV5 transcription, but repress GATA6 and NOTCH3 expression. ETV5, GATA6 and NOTCH3 are the candidate targets of LMP2A in gastric cancer.