EB病毒（EBV）在相关性肿瘤如鼻咽癌（NPC）中为保持潜伏感染状态调控其基因表达机制仍不很清楚，长非编码RNA（lncRNA）被EBV利用调节基因表达尚无报道。我们前期发现EBV感染细胞和NPC组织中lncRNA BC200表达上调；预测和初步实验结果提示，BC200可结合并促进翻译起始因子eIF4A3蛋白水平而抑制EBV基因表达，BC200表达可能受STATs调节。本项目拟在确认BC200与eIF4A3结合基础上，研究BC200通过泛素化蛋白酶体途径稳定eIF4A3表达、由eIF4A3调节基因表达；研究STATs在上游结合BC200基因启动子区从而上调BC200表达、影响下游基因表达的机制；在移植瘤和鼻咽癌临床样本中验证STATs/BC200/eIF4A3轴关键分子间表达关系。本研究为了解EBV自限性基因表达及其在鼻咽癌发生中的作用提供理论基础，为NPC诊断治疗提供潜在分子标志物。

Epstein-Barr virus (EBV) is a causative agent of several malignancies such as nasopharyngeal carcinoma (NPC). In order to maintain its latent infection status, the viral gene expression is highly restricted with the regulation mechanism largely unknown. Long non-coding RNAs (lncRNAs) are emerging and powerful regulators which have been demonstrated to play crucial roles in cancer development. There is no report whether and how a lncRNA is hijacked by EBV to modulate the viral gene expression currently. In our previous work, based on genome-wide RNA sequencing (RNAseq), we examined lncRNA expression profiles in four EBV genome-infected human embryonic kedney epihtelial cell lines, and found the abnormal differential expression of lncRNA BC200 compared with EBV-negative cells. The upregulation was identified in more EBV-positive cell lines and clinical NPC tissues. Bioinformatics analysis and preliminary experiments gave the clue that BC200 could bind to the translation initiation factor eIF4A3, promote the protein level of eIF4A3, and inhibit the EBV gene expression. BC200 gene expression was predicted to be regulated by transcriptional factors STATs, which are also crucial signallings activated by EBV. In this study, based on the identification of the BC200-eIF4A3 combination, whether BC200 could stabilize eIF4A3 through the ubiquitin-proteasome pathway would be investigated. How the viral gene expression is to be influenced by the eIF4A3 level would be also analyzed. The expression of downstream genes would be studied following the BC200/eIF4A3 expression imbalance. The expression relationship of the STATs/BC200/eIF4A3 axis would be validated in xenograft tissues derived from EBV-positive cells and clinical NPC specimens. The study in this project would help us to better understand the viral pathogenesis from a new insight, thus providing novel potential biomarkers and basic theory in virus-targeted diagnosis and therapeutics of EBV-associated NPC.