Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266021, People's Republic of China.
Department of Clinical Laboratory, Zibo Central Hospital, ZiBo, 255036, China.
Virus Genes. 2023 Oct;59(5):703-715. doi: 10.1007/s11262-023-02023-w. Epub 2023 Aug 3.
Epstein-Barr virus (EBV) is a human tumor-associated virus that encodes various microRNAs. EBV infection causes a variety of malignant tumors, including nasopharyngeal carcinoma and gastric cancer, etc. EBV-associated gastric cancer (EBVaGC) has unique molecular characteristics from other gastric cancers, but its pathogenic mechanism remains unclear. In recent years, erythropoietin-producing human hepatocellular 2 (EphA2) has been reported to be highly expressed in various cancers and promote tumor growth and metastasis. As an important cancer oncogene, EphA2 is a potential therapeutic target. However, whether EBV is involved in the regulation of EphA2 and thus affects the progression of EBVaGC remains unclear. In this study, we found that the expression of EphA2 in EBVaGC cells was significantly lower than that in EBV-negative gastric cancer (EBVnGC) cells. Additionally, overexpression of EphA2 in EBVaGC cells promoted migration and proliferation, and inhibited autophagy. EBV-miR-BART1-3p and BART18-5p were found to target the 3'-UTR of EphA2 and down-regulate its expression. Our results suggest that EBV may be involved in gastric cancer progression by targeting EphA2 through BART1-3p and BART18-5p.
EB 病毒（EBV）是一种与人类肿瘤相关的病毒，可编码多种 microRNAs。EBV 感染可引起多种恶性肿瘤，包括鼻咽癌和胃癌等。EBV 相关胃癌（EBVaGC）与其他胃癌具有独特的分子特征，但发病机制尚不清楚。近年来，促红细胞生成素产生肝细胞 2（EphA2）已被报道在多种癌症中高表达，并促进肿瘤生长和转移。作为重要的癌症致癌基因，EphA2 是一个潜在的治疗靶点。然而，EBV 是否参与 EphA2 的调节，从而影响 EBVaGC 的进展尚不清楚。在本研究中，我们发现 EphA2 在 EBVaGC 细胞中的表达明显低于 EBV 阴性胃癌（EBVnGC）细胞。此外，在 EBVaGC 细胞中过表达 EphA2 可促进迁移和增殖，并抑制自噬。发现 EBV-miR-BART1-3p 和 BART18-5p 可靶向 EphA2 的 3'-UTR 并下调其表达。我们的研究结果表明，EBV 可能通过 BART1-3p 和 BART18-5p 靶向 EphA2 参与胃癌的进展。
