{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:04:45Z","timestamp":1780376685775,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,3,5]],"date-time":"2013-03-05T00:00:00Z","timestamp":1362441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2013,3,5]],"date-time":"2013-03-05T00:00:00Z","timestamp":1362441600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"vor","delay-in-days":453,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":910,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["molecularoncology.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:p>C13ORF18 is frequently hypermethylated in cervical cancer but not in normal cervix and might serve as a biomarker for the early detection of cervical cancer in scrapings. As hypermethylation is often observed for silenced tumor suppressor genes (TSGs), hypermethylated biomarker genes might exhibit tumor suppressive activities upon re\u2010expression. Epigenetic drugs are successfully exploited to reverse TSG silencing, but act genome\u2010wide. Artificial Transcription Factors (ATFs) provide a gene\u2010specific approach for re\u2010expression of silenced genes. Here, we investigated the potential tumor suppressive role of C13ORF18 in cervical cancer by ATF\u2010induced re\u2010expression.<\/jats:p><jats:p>Five zinc finger proteins were engineered to bind the C13ORF18 promoter and fused to a strong transcriptional activator. C13ORF18 expression could be induced in cervical cell lines: ranging from &gt;40\u2010fold in positive (C13ORF18\u2010unmethylated) cells to &gt;110\u2010fold in negative (C13ORF18\u2010methylated) cells. Re\u2010activation of C13ORF18 resulted in significant cell growth inhibition and\/or induction of apoptosis. Co\u2010treatment of cell lines with ATFs and epigenetic drugs further enhanced the ATF\u2010induced effects. Interestingly, re\u2010activation of C13ORF18 led to partial demethylation of the C13ORF18 promoter and decreased repressive histone methylation. These data demonstrate the potency of ATFs to re\u2010express and potentially demethylate hypermethylated silenced genes. Concluding, we show that C13ORF18 has a TSG function in cervical cancer and may serve as a therapeutic anti\u2010cancer target. As the amount of epimutations in cancer exceeds the number of gene mutations, ATFs provide promising tools to validate hypermethylated marker genes as therapeutic targets.<\/jats:p>","DOI":"10.1016\/j.molonc.2013.02.017","type":"journal-article","created":{"date-parts":[[2013,3,6]],"date-time":"2013-03-06T01:17:37Z","timestamp":1362532657000},"page":"669-679","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":39,"title":["Functional validation of putative tumor suppressor gene <i>C13ORF18<\/i> in cervical cancer by Artificial Transcription Factors"],"prefix":"10.1002","volume":"7","author":[{"given":"Christian","family":"Huisman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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Published by Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}