EB 病毒 (EBV) 与淋巴瘤和上皮瘤有关，但缺乏专门针对 EBV 阳性肿瘤的药物。 BamHI A 右向转录 (BART) miRNA 在所有 EBV 阳性肿瘤中表达，抑制裂解性感染和宿主细胞凋亡。我们发现辛二酰苯胺异羟肟酸 (SAHA)（一种组蛋白脱乙酰酶抑制剂）可以作为抑制 BART 启动子活性和 BART miRNA 转录的药物。与 EBV 阴性细胞相比，SAHA 治疗对 EBV 阳性细胞的细胞增殖具有更明显的抑制作用，影响 p53 野生型和突变型胃上皮细胞。 SAHA 处理增强了野生型 EBV 感染细胞的裂解感染，同时也增强了 BZLF1 缺陷的 EBV 感染细胞的细胞死亡。它使 BART 基因表达降低 85%，并增加 BART miRNA 靶向的促凋亡因子的表达。这些发现表明，SAHA 不仅诱导裂解性感染，还通过抑制 BART miRNA 转录和促进细胞凋亡程序导致细胞死亡。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Epstein-Barr virus (EBV) is linked to lymphoma and epithelioma but lacks drugs specifically targeting EBV-positive tumors. BamHI A Rightward Transcript (BART) miRNAs are expressed in all EBV-positive tumors, suppressing both lytic infection and host cell apoptosis. We identified suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylase enzymes, as an agent that suppresses BART promoter activity and transcription of BART miRNAs. SAHA treatment demonstrated a more pronounced inhibition of cell proliferation in EBV-positive cells compared to EBV-negative cells, affecting both p53 wild-type and mutant gastric epithelial cells. SAHA treatment enhanced lytic infection in wild-type EBV-infected cells, while also enhancing cell death in BZLF1-deficient EBV-infected cells. It reduced BART gene expression by 85% and increased the expression of proapoptotic factors targeted by BART miRNAs. These findings suggest that SAHA not only induces lytic infection but also leads to cell death by suppressing BART miRNA transcription and promoting the apoptotic program.Copyright © 2024 Elsevier Inc. All rights reserved.