人源微小RNA-7974通过直接靶向……抑制爱泼斯坦-巴尔病毒再激活。（原文中“and”后面内容缺失）

Hsa-miR-7974 Suppresses Epstein-Barr Virus Reactivation by Directly Targeting and .

作者信息

Li Haotian, Wang Hui, Wang Jiao, Lu Xuexin, Zhang Jieqiong, Wang Mingming, Yu Dongbo, Li Ying, Wang Shiwen

机构信息

National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

出版信息

Viruses. 2025 Apr 23;17(5):594. doi: 10.3390/v17050594.

DOI:10.3390/v17050594

PMID:40431607

Abstract

Epstein-Barr virus (EBV) reactivation, a key factor in Epstein-Barr virus (EBV)-associated malignancies, is regulated by specific cellular microRNAs (miRNAs). This study investigated the role of Hsa-miR-7974 (miR-7974) in this process. miRNA sequencing revealed significant downregulation of miR-7974 in reactivated EBV-positive cell lines (Raji and C666-1). Bioinformatics prediction and dual-luciferase assays confirmed the direct targeting of the EBV immediate-early gene BRLF1 by miR-7974. Furthermore, miR-7974 mimics suppressed, whereas inhibitors increased, the expression of key EBV lytic genes (BZLF1, BRLF1, and BMRF1) and the viral load, as validated by RT-qPCR. Bioinformatics analyses revealed the involvement of miR-7974 in cellular pathways such as membrane dynamics and signal transduction (MAPK, NF-κB, and IL-10), and its association with Hodgkin's lymphoma, leukemia, and nasopharyngeal neoplasms. These findings establish that miR-7974 functions as a crucial negative regulator of EBV reactivation by directly targeting BRLF1, highlighting its potential significance in the pathogenesis of EBV-associated malignancies.

摘要

爱泼斯坦-巴尔病毒（EBV）再激活是爱泼斯坦-巴尔病毒（EBV）相关恶性肿瘤的关键因素，受特定细胞微小RNA（miRNA）调控。本研究调查了Hsa-miR-7974（miR-7974）在此过程中的作用。miRNA测序显示，在再激活的EBV阳性细胞系（Raji和C666-1）中，miR-7974显著下调。生物信息学预测和双荧光素酶测定证实miR-7974直接靶向EBV即刻早期基因BRLF1。此外，经RT-qPCR验证，miR-7974模拟物抑制而抑制剂增加关键EBV裂解基因（BZLF1、BRLF1和BMRF1）的表达及病毒载量。生物信息学分析显示，miR-7974参与细胞途径，如膜动力学和信号转导（MAPK、NF-κB和IL-10），并与霍奇金淋巴瘤、白血病和鼻咽肿瘤相关。这些发现表明，miR-7974通过直接靶向BRLF1作为EBV再激活的关键负调节因子，突出了其在EBV相关恶性肿瘤发病机制中的潜在重要性。