Yin Qinyan, Flemington Erik K
Tulane Health Sciences Center and Tulane Cancer Center, Department of Pathology, SL79, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Virology. 2006 Mar 15;346(2):385-93. doi: 10.1016/j.virol.2005.11.021. Epub 2005 Dec 15.
The Epstein Barr virus (EBV) plays a role in maintenance of the tumor phenotype in a number of human cancers. The EBV latency replication factor, EBNA1, is required for persistence of the EBV episome, is anti-apoptotic, and is universally expressed in all EBV-associated tumors. Here, we show that EBNA1-specific siRNAs can inhibit EBNA1 expression and function. siRNAs were generated against three target sites in the EBNA1 messenger RNA, and two of these were found to inhibit EBNA1 expression from an ectopic EBNA1 expression cassette. EBNA1 siRNAs also inhibit endogenously expressed EBNA1 in EBV-positive epithelial and B-cell lines. Using a mini-EBV replication model, siRNA-mediated inhibition of EBNA1 expression suppressed the episomal maintenance function of EBNA1. Lastly, introduction of an EBNA1 siRNA into an EBV-positive tumor cell line inhibited tumor cell growth/survival. These data suggest that siRNAs against EBNA1 may have therapeutic value in EBV-associated diseases.
爱泼斯坦-巴尔病毒（EBV）在多种人类癌症的肿瘤表型维持中发挥作用。EBV潜伏复制因子EBNA1是EBV附加体持续存在所必需的，具有抗凋亡作用，且在所有EBV相关肿瘤中均普遍表达。在此，我们表明针对EBNA1的小干扰RNA（siRNA）可抑制EBNA1的表达和功能。针对EBNA1信使RNA中的三个靶位点生成了siRNA，其中两个被发现可抑制来自异位EBNA1表达盒的EBNA1表达。EBNA1 siRNA还可抑制EBV阳性上皮细胞系和B细胞系中内源性表达的EBNA1。使用微型EBV复制模型，siRNA介导的EBNA1表达抑制作用抑制了EBNA1的附加体维持功能。最后，将EBNA1 siRNA导入EBV阳性肿瘤细胞系可抑制肿瘤细胞的生长/存活。这些数据表明，针对EBNA1的siRNA可能在EBV相关疾病中具有治疗价值。
