EB病毒致癌作用主要通过影响受感染细胞的基因表达及相应的生物学行为而实现，但其致癌机制尚未完全明了。我们前期研究发现在EBV阳性胃癌和鼻咽癌细胞系中长链非编码RNA H19可能是EBV作用的靶基因。本研究拟比较EBV阳性和阴性胃癌组织及相应癌旁组织、NPC和鼻咽部良性粘膜病变组织中H19基因启动子和印记控制区甲基化、印记状态及表达的异同，分析彼此间相互关系以及与肿瘤各临床指标的相关性；观察EBV编码基因对H19基因表达表观遗传调控因素的影响，旨在明确EBV调控H19基因表达的机制和临床意义。为阐明EBV参与相关肿瘤发生发展的机制，寻找EBV相关胃癌和鼻咽癌的特异分子标志物提供理论和实验依据。

The oncogenic mechanism of Epstein-Barr virus (EBV) remains unclear. Our preliminary data demonstrated that the H19 long noncoding RNA, an imprinted gene, may be EBV-driven suppressed gene in EBV-positive gastric carcinoma (GC) and nasopharyngeal carcinoma (NPC) cell lines. To investigate the regulatory mechanism of EBV on expression of H19 in the EBV-positive GC and NPC, the CpG methylation in the promoter and the imprinting control region 1 of H19, the imprinting status and expression of H19 in EBV-positive and -negative GC tissues and their matched adjacent normal gastric tissues, as well as in NPC tissues and nasopharyngeal tissues from non-tumor patients, will be evaluated and their interplay and clinical associations will be investigated. The regulatory factors associated with the epigenetic silences of H19 expression will be detected in EBV-negative GC and NPC cell lines with overexpression of EBV-encoded latent genes (LMP1, LMP2A, EBERs or EBNA1) and in EBV-positive GC and NPC cell lines with knocking-down LMP1, LMP2A, EBERs or EBNA1. To elucidate the molecular functions and the regulatory mechanisms of H19 in the development and progression of EBV-positive GC and NPC, the gain and loss of gene function assay will be conducted by in vitro and in vivo gene transfection studies. The results from this study will provide theoretic and experimental evidence to better understand the carcinogenesis mechanisms of EBV in the development of EBV-associated tumors, and may help to identify new molecular markers for occurrence, metastasis and prognosis of EBV-positive GC and NPC.