{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T11:07:12Z","timestamp":1777720032027,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,6,21]],"date-time":"2018-06-21T00:00:00Z","timestamp":1529539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007899","name":"University of Arizona","doi-asserted-by":"publisher","award":["P30 CA023074"],"award-info":[{"award-number":["P30 CA023074"]}],"id":[{"id":"10.13039\/100007899","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":[[2018,8]]},"abstract":"<jats:p>Long interspersed nuclear element\u20101 (<jats:styled-content style=\"fixed-case\">LINE<\/jats:styled-content>\u20101 or <jats:italic>L1<\/jats:italic>) reactivation is linked to poor prognosis in non\u2010small\u2010cell lung carcinoma (<jats:styled-content style=\"fixed-case\">NSCLC<\/jats:styled-content>), but the molecular bases of this response remain largely unknown. In this report, we show that challenge of human bronchial epithelial cells (<jats:styled-content style=\"fixed-case\">HBEC<\/jats:styled-content>s) with the lung carcinogen, benzo(a)pyrene (BaP), shifted the <jats:italic>L1<\/jats:italic> promoter from a heterochromatic to euchromatic state through disassembly of the nucleosomal and remodeling deacetylase (Nu<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>) complex. Carcinogen challenge was also associated with partial displacement of constituent proteins from the nuclear to the cytoplasmic compartment. Disruption of Nu<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content> corepression by genetic ablation or carcinogen treatment correlated with accumulation of <jats:italic>L1 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and proteins. Mi2\u03b2 bound directly to the <jats:italic>L1<\/jats:italic> promoter to effect retroelement silencing, and this response required the <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010 and <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase\u2010binding domains of Mi2\u03b2. Sustained expression of <jats:italic>L1<\/jats:italic> in <jats:styled-content style=\"fixed-case\">HBEC<\/jats:styled-content>s was tumorigenic in a human\u2013<jats:styled-content style=\"fixed-case\">SCID<\/jats:styled-content> mouse xenograft model, giving rise to tumors that regressed over time. Together, these results show that functional modulation of the Nu<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content> constituent proteins is a critical molecular event in the activation of <jats:italic>L1<\/jats:italic> retrotransposon. <jats:italic>L1<\/jats:italic> expression creates a microenvironment in <jats:styled-content style=\"fixed-case\">HBEC<\/jats:styled-content>s that is conducive to neoplasia and malignant transformation.<\/jats:p>","DOI":"10.1002\/1878-0261.12329","type":"journal-article","created":{"date-parts":[[2018,5,30]],"date-time":"2018-05-30T08:06:09Z","timestamp":1527667569000},"page":"1342-1357","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Epigenetic reactivation of <scp>LINE<\/scp>\u20101 retrotransposon disrupts Nu<scp>RD<\/scp> corepressor functions and induces oncogenic transformation in human bronchial epithelial cells"],"prefix":"10.1002","volume":"12","author":[{"suffix":"Jr.","given":"Pasano","family":"Bojang","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine University of Arizona College of Medicine Tucson AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth S.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine University of Arizona College of Medicine Tucson AZ USA"},{"name":"Center for Applied Genetics and Genomic Medicine University of Arizona Health Sciences Tucson AZ 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