研究动态
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miR-BART1-3p和BART18-5p通过靶向EPO2来抑制巨细胞病毒相关胃癌细胞的迁移、增殖并激活自噬。

MiR-BART1-3p and BART18-5p inhibit cell migration, proliferation and activate autophagy in Epstein-Barr virus-associated gastric cancer by targeting erythropoietin-producing human hepatocellular 2.

发表日期:2023 Aug 03
作者: Duo Shi, Wen Liu, Xing Zhang, Yan Zhang, Bing Luo
来源: GENES & DEVELOPMENT

摘要:

爱普斯坦-巴尔病毒(EBV)是一种与人类肿瘤相关的病毒,编码多种微小RNA。EBV感染会引发多种恶性肿瘤,包括鼻咽癌和胃癌等。EBV相关胃癌(EBVaGC)具有与其他胃癌不同的分子特征,但其致病机制尚不清楚。近年来,人红细胞生成素2(EphA2)在多种癌症中高度表达,并促进肿瘤生长和转移。作为一种重要的癌症致病基因,EphA2是一个潜在的治疗靶点。然而,EBV是否参与EphA2的调控以及如何影响EBVaGC的进展仍不清楚。在本研究中,我们发现在EBVaGC细胞中,EphA2的表达显著低于EBV阴性胃癌(EBVnGC)细胞。此外,EphA2在EBVaGC细胞中过表达促进了细胞的迁移和增殖,并抑制了自噬。EBV-miR-BART1-3p和BART18-5p可靶向EphA2的3'-UTR,并下调其表达。我们的结果表明,EBV可能通过BART1-3p和BART18-5p靶向EphA2参与胃癌的进展。© 2023. 作者,独家授权给 Springer Science+Business Media, LLC, Springer Nature的一部分。
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.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.