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However, understanding the regulation and function of <jats:italic>ZIC4<\/jats:italic> in pediatric choroid plexus tumors (CPTs) remained limited. This study employed data mining and bioinformatics analysis to investigate the DNA methylation status of <jats:italic>ZIC4<\/jats:italic> in CPTs and its correlation with patient survival. Our results unveiled <jats:italic>ZIC4<\/jats:italic> methylation as a segregating factor, dividing CPT cohorts into two clusters, with hyper-methylation linked to adverse prognosis. Hyper-methylation of <jats:italic>ZIC4<\/jats:italic> was confirmed in a choroid plexus carcinoma-derived cell line (CCHE-45) by bisulfite sequencing. Furthermore, our study demonstrated that demethylating agent and a histone methyltransferase inhibitor could reverse <jats:italic>ZIC4<\/jats:italic> silencing. RNA sequencing and proteomic analysis showed that <jats:italic>ZIC4<\/jats:italic> over-expression influenced genes and proteins involved in immune response, antigen processing and presentation, endoplasmic reticulum stress, and metabolism. Functionally, re-expressing <jats:italic>ZIC4<\/jats:italic> negatively impacted cell proliferation and migration. Ultimately, these findings underscore <jats:italic>ZIC4<\/jats:italic> hyper-methylation as a prognostic marker in CPTs and shed light on potential mechanisms underlying its tumor suppressor role in CPC. This insight paves the way for novel therapeutic targets in treating aggressive CPTs.<\/jats:p>","DOI":"10.1038\/s41598-024-71188-7","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T07:23:29Z","timestamp":1726125809000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Epigenetic silencing of ZIC4 unveils a potential tumor suppressor role in pediatric choroid plexus carcinoma"],"prefix":"10.1038","volume":"14","author":[{"given":"Dina","family":"Hesham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Mosaab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Amer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouran","family":"Al-Shehaby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameh","family":"Magdeldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hristo","family":"Georgiev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisham","family":"Elshoky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Rady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled Abou","family":"Aisha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Sabet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6465-9881","authenticated-orcid":false,"given":"Shahenda","family":"El-Naggar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,12]]},"reference":[{"issue":"6","key":"71188_CR1","doi-asserted-by":"publisher","first-page":"993","DOI":"10.5858\/2008-132-993-SNUARO","volume":"132","author":"DJ Brat","year":"2008","unstructured":"Brat, D. 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