# Hsa-miR-7974 Suppresses Epstein-Barr Virus Reactivation by Directly Targeting BZLF1 and BRLF1

## TL;DR

This study shows that the microRNA Hsa-miR-7974 prevents the reactivation of Epstein-Barr virus by targeting key viral genes, which could be important for understanding related cancers.

## Contribution

The novel contribution is identifying miR-7974 as a direct suppressor of EBV reactivation through targeting BRLF1 and BZLF1.

## Key findings

- miR-7974 is significantly downregulated in EBV-reactivated cell lines.
- miR-7974 directly targets and suppresses EBV lytic genes BRLF1 and BZLF1.
- miR-7974 is linked to pathways involved in EBV-associated malignancies like Hodgkin’s lymphoma and nasopharyngeal neoplasms.

## 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.