{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:40:20Z","timestamp":1792183220807,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,8,21]],"date-time":"2018-08-21T00:00:00Z","timestamp":1534809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005716","name":"Babol University of Medical Sciences","doi-asserted-by":"publisher","award":["9440843"],"award-info":[{"award-number":["9440843"]}],"id":[{"id":"10.13039\/501100005716","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Gastric cancer (GC) is one of the most common causes of cancer\u2010related death in the world, with multiple genetic and epigenetic alterations involved in disease development.\n                    <jats:italic>CYLD<\/jats:italic>\n                    tumor suppressor gene encodes a multifunctional deubiquitinase which negatively regulates various signaling pathways. Deregulation of this gene has been found in different types of cancer. This study aimed to evaluate for the first time the CpG island methylation pattern of\n                    <jats:italic>CYLD<\/jats:italic>\n                    gene promoter, and its expression level in gastric adenocarcinoma.\n                    <jats:italic>CYLD<\/jats:italic>\n                    messenger RNA expression and promoter methylation in 53 tumoral and their non\u2010neoplastic counterpart tissues were assessed using quantitative polymerase chain reaction and bisulfite sequencing. Also, we investigated the impacts of the infectious agents including\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    (\n                    <jats:italic>H. pylori<\/jats:italic>\n                    ), EBV, and CMV on\n                    <jats:italic>CYLD<\/jats:italic>\n                    expression and promoter methylation in GC. Results showed that the expression level of\n                    <jats:italic>CYLD<\/jats:italic>\n                    was downregulated in GC, and was significantly associated with gender (female), patient\u2019s age (&lt;60), high grade, and no lymph\u2010node metastasis (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001, 0.002, 0.03, and 0.003, respectively). Among the 31 analyzed CpG sites located in about 600\u2009bp region within the promoter, two CpG sites were hypermethylated in GC tissues. We also found a significant inverse association between DNA promoter methylation and\n                    <jats:italic>CYLD<\/jats:italic>\n                    expression (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02). Furthermore, a direct association between\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    , EBV, and CMV infections with hypermethylation and reduced\n                    <jats:italic>CYLD<\/jats:italic>\n                    expression was observed (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04, 0.03, and 0.03, respectively). Our findings indicate that\n                    <jats:italic>CYLD<\/jats:italic>\n                    is downregulated in GC. Infectious agents may influence\n                    <jats:italic>CYLD<\/jats:italic>\n                    expression.\n                  <\/jats:p>","DOI":"10.1002\/jcp.27220","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T12:11:03Z","timestamp":1534939863000},"page":"4115-4124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Epigenetic alterations of\n                    <i>CYLD<\/i>\n                    promoter modulate its expression in gastric adenocarcinoma: A footprint of infections"],"prefix":"10.1002","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7068-7811","authenticated-orcid":false,"given":"Elham","family":"Ghadami","sequence":"first","affiliation":[{"name":"Department of Genetics, Faculty of Medicine Babol University of Medical Sciences Babol Iran"},{"name":"Department of Genetics Cellular and Molecular Biology Research Center, Health 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