{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:52:32Z","timestamp":1787003552506,"version":"build-2736575974"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T00:00:00Z","timestamp":1577404800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T00:00:00Z","timestamp":1577404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Aberrant differentiation, driven by activation of normally silent tissue-specific genes, results in a switch of cell identity and often leads to cancer progression. The underlying genetic and epigenetic events are largely unexplored. Here, we report ectopic activation of the hepatobiliary-, intestinal- and neural-specific gene one cut homeobox 2 (\n                    <jats:italic>ONECUT2)<\/jats:italic>\n                    in various subtypes of lung cancer. ONECUT2 expression was associated with poor prognosis of RAS-driven lung adenocarcinoma. ONECUT2 overexpression promoted the malignant growth and invasion of A549 lung cancer cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    , as well as xenograft tumorigenesis and bone metastases of these cells\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Integrative transcriptomics and epigenomics analyses suggested that ONECUT2 promoted the trans-differentiation of lung cancer cells by preferentially targeting and regulating the activity of bivalent chromatin domains through modulating Polycomb Repressive Complex 2 (PRC2) occupancy. Our findings demonstrate that ONECUT2 is a lineage-specific and context-dependent oncogene in lung adenocarcinoma and suggest that ONECUT2 is a potential therapeutic target for these tumors.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-56277-2","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T06:02:42Z","timestamp":1577426562000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["ONECUT2 overexpression promotes RAS-driven lung adenocarcinoma progression"],"prefix":"10.1038","volume":"9","author":[{"given":"Qingyang","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huichun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2980-5166","authenticated-orcid":false,"given":"Guohong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Landian","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyin","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,27]]},"reference":[{"key":"56277_CR1","doi-asserted-by":"publisher","first-page":"5771","DOI":"10.1038\/onc.2015.85","volume":"34","author":"WK Cheung","year":"2015","unstructured":"Cheung, W. 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