Abstract：
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.
摘要：
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向右转录本（BART）miRNA在所有EBV阳性肿瘤中表达，抑制裂解感染和宿主细胞凋亡。我们鉴定了辛二酰苯胺异羟肟酸（SAHA），组蛋白脱乙酰酶的抑制剂，作为抑制BART启动子活性和BARTmiRNA转录的试剂。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治疗增强了野生型EBV感染细胞的裂解感染，同时还增强BZLF1缺陷型EBV感染细胞的细胞死亡。它使BART基因表达减少了85％，并增加了BARTmiRNA靶向的促凋亡因子的表达。这些发现表明，SAHA不仅诱导裂解感染，而且通过抑制BARTmiRNA转录和促进凋亡程序导致细胞死亡。
