Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Department of Clinical Laboratory, Qingdao Women and Children's Hospital, Qingdao, 266034, China.
Virus Genes. 2022 Dec;58(6):515-526. doi: 10.1007/s11262-022-01925-5. Epub 2022 Jul 11.
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.
EB 病毒（EBV）是一种众所周知的人类致癌病毒。然而，其在 EBV 相关胃癌（EBVaGC）的发生和发展中的分子机制仍知之甚少。潜伏膜蛋白 2A（LMP2A）是 EBV 潜伏相关蛋白，在部分 EBVaGC 病例中表达。本研究通过对表达 LMP2A 的胃癌细胞系 SGC7901 进行转录组测序，分析了 LMP2A 对胃癌细胞基因表达的影响。该研究共监测到 238 个表达差异显著的基因，其中上调基因 101 个，下调基因 137 个。通过 KEGG 通路分析发现，更多的基因富集在甾体生物合成、轴突导向和萜类骨架生物合成通路中，而在 PI3K-Akt 和 AMPK 信号通路中分别有 5 个基因富集，均有显著意义。这表明 LMP2A 可能参与细胞生物合成，并通过 AKT 和 AMPK 信号通路影响下游基因和细胞生物学行为。进一步评估证实，LMP2A 诱导 ETV5 转录，但抑制 GATA6 和 NOTCH3 的表达。ETV5、GATA6 和 NOTCH3 是 LMP2A 在胃癌中的候选靶标。
