title: Epigenetic silencing of WNT5A in Epstein-Barr virus-associated gastric carcinoma.
abstract: 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. WNT5A expression 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 of WNT5A but a high level of methylation in the promoter region. In contrast, EBV-negative GC had higher WNT5A expression and a lower level of promoter methylation. The reduced WNT5A expression could be restored by treatment with Aza, a methyltransferase inhibitor. Increased expression of WNT5A in vitro inhibited β-catentin expression in EBVaGC cells (SNU719). These results suggest that hypermethylation of WNT5A induced by EBV may contribute to the development of EBVaGC. Ectopic introduction of WNT5A may have preventive/therapeutic potential for tumors with silenced WNT5A.
authors.affiliation: Department of Medical Microbiology, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Sun
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Tao
authors.forename: Bing
authors.initials: B
authors.lastname: Luo
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D057890:Epigenomics; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D005260:Female; D020868:Gene Silencing; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein