{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:55:04Z","timestamp":1772117704711,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001273","name":"CHILDREN with CANCER UK","doi-asserted-by":"publisher","award":["2012\/135"],"award-info":[{"award-number":["2012\/135"]}],"id":[{"id":"10.13039\/501100001273","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:p>\n                    Wilms tumour (WT), an embryonal kidney cancer, has been extensively characterised for genetic and epigenetic alterations, but a proportion of WTs still lack identifiable abnormalities. To uncover DNA methylation changes critical for WT pathogenesis, we compared the epigenome of foetal kidney with two WT cell lines, filtering our results to remove common cancer\u2010associated epigenetic changes and to enrich for genes involved in early kidney development. This identified four hypermethylated genes, of which\n                    <jats:italic>ESRP2<\/jats:italic>\n                    (epithelial splicing regulatory protein 2) was the most promising for further study.\n                    <jats:italic>ESRP2<\/jats:italic>\n                    was commonly repressed by DNA methylation in WT, and this occurred early in WT development (in nephrogenic rests).\n                    <jats:italic>ESRP2<\/jats:italic>\n                    expression was reactivated by DNA methyltransferase inhibition in WT cell lines. When\n                    <jats:italic>ESRP2<\/jats:italic>\n                    was overexpressed in WT cell lines, it inhibited cellular proliferation\n                    <jats:italic>in\u2009vitro<\/jats:italic>\n                    , and\n                    <jats:italic>in\u2009vivo<\/jats:italic>\n                    it suppressed tumour growth of orthotopic xenografts in nude mice. RNA\u2010seq of the ESRP2\u2010expressing WT cell lines identified several novel splicing targets. We propose a model in which epigenetic inactivation of\n                    <jats:italic>ESRP2<\/jats:italic>\n                    disrupts the mesenchymal to epithelial transition in early kidney development to generate WT.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13101","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T12:01:30Z","timestamp":1631620890000},"page":"630-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The epithelial splicing regulator\n                    <i>ESRP2<\/i>\n                    is epigenetically repressed by DNA hypermethylation in Wilms tumour and acts as a tumour suppressor"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3897-5861","authenticated-orcid":false,"given":"Danny","family":"Legge","sequence":"first","affiliation":[{"name":"School of Cellular and Molecular Medicine University of 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