Epigenetic silencing of WNT5A in Epstein-Barr virus-associated gastric carcinoma
Epigenetic silencing of WNT5A in Epstein-Barr virus-associated gastric carcinoma
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DOI：
10.1007/s00705-012-1481-x
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发表时间：
2012
影响因子：
2.7
通讯作者：
Xia Liu;Yun Wang;Xiaofeng Wang;Zhi-fu Sun;Lili Li;Q. Tao;B. Luo
中科院分区：
文献类型：
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作者：
Xia Liu;Yun Wang;Xiaofeng Wang;Zhi-fu Sun;Lili Li;Q. Tao;B. Luo
eb病毒（EBV）可导致多种肿瘤的发生，包括EBV相关的胃癌（EBVaGC），但其在EBVaGC中的作用机制尚不清楚。在5株ebv阳性和15株ebv阴性的GC细胞株中检测了wnt5a的表达和启动子甲基化。我们还检测了23例ebv阳性和25例ebv阴性配对肿瘤/正常组织样本的甲基化状态。ebv阳性GC中wnt5不表达或极低表达，但在启动子区域有高水平的甲基化。相比之下，ebv阴性GC具有较高的wnt5a表达和较低的启动子甲基化水平。甲基转移酶抑制剂Aza可以恢复wnt5a的表达。体外wnt5ain表达增加抑制EBVaGC细胞中β-catentin表达（SNU719）。这些结果表明，EBV诱导的wnt5高甲基化可能有助于EBVaGC的发展。异位引入wnt5可能对沉默wnt5a的肿瘤具有预防/治疗潜力。
Epstein-Barr virus (EBV) is responsible for the development of multiple tumors, including EBV-associated gastric carcinoma (EBVaGC), but little is known about its mechanisms in EBVaGC.WNT5Aexpression and promoter methylation were measured in 5 EBV-positive and 15 EBV-negative GC cell lines. The methylation status of 23 EBV-positive and 25 EBV-negative paired tumor/normal tissue samples was also examined. EBV-positive GC had no or very low expression ofWNT5Abut a high level of methylation in the promoter region. In contrast, EBV-negative GC had higherWNT5Aexpression and a lower level of promoter methylation. The reducedWNT5Aexpression could be restored by treatment with Aza, a methyltransferase inhibitor. Increased expression ofWNT5Ain vitroinhibited β-catentin expression in EBVaGC cells (SNU719). These results suggest that hypermethylation ofWNT5Ainduced by EBV may contribute to the development of EBVaGC. Ectopic introduction ofWNT5Amay have preventive/therapeutic potential for tumors with silencedWNT5A.