{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:16:11Z","timestamp":1790741771442,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":280,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01BX000130"],"award-info":[{"award-number":["I01BX000130"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Alterations in RNA splicing are associated with cancer, but it is not clear whether they result from malignant transformation or have a causative role. We show here that hepatocyte\u2010specific deletion of serine\/arginine\u2010rich splicing factor 3 (SRSF3) impairs hepatocyte maturation and metabolism in early adult life, and mice develop spontaneous hepatocellular carcinoma (HCC) with aging. Tumor development is preceded by chronic liver disease with progressive steatosis and fibrosis. SRSF3 protects mice against CCl<jats:sub>4<\/jats:sub>\u2010induced fibrosis and carcinogenesis and suppresses inclusion of the profibrogenic EDA exon in fibronectin 1. Loss of SRSF3 increases expression of insulin\u2010like growth factor 2 and the A\u2010isoform of the insulin receptor, allowing aberrant activation of mitogenic signaling, promotes aberrant splicing and expression of epithelial to mesenchymal transition (EMT) genes, and activates Wnt\/\u03b2\u2010catenin signaling leading to c\u2010Myc induction. Finally, SRSF3 expression is either decreased or the protein mislocalized in human HCC. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Our data suggest a potential role for SRSF3 in preventing hepatic carcinogenesis by regulating splicing to suppress fibrosis, mitogenic splicing, and EMT. Thus, these mice may provide an attractive model to discover the pathogenic mechanisms linking aberrant pre\u2013messenger RNA splicing with liver damage, fibrosis, and HCC. (H<jats:sc>epatology<\/jats:sc> 2015;61:171\u2013183)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.27380","type":"journal-article","created":{"date-parts":[[2014,8,18]],"date-time":"2014-08-18T08:09:35Z","timestamp":1408349375000},"page":"171-183","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":108,"title":["Deletion of serine\/arginine\u2010rich splicing factor 3 in hepatocytes predisposes to hepatocellular carcinoma in mice"],"prefix":"10.1097","volume":"61","author":[{"given":"Supriya","family":"Sen","sequence":"first","affiliation":[{"name":"Medical Research Service,VA San Diego Healthcare System,San Diego,CA"},{"name":"Department of Medicine, Division of Endocrinology and Metabolism,University of California San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda","family":"Langiewicz","sequence":"additional","affiliation":[{"name":"Medical Research Service,VA San Diego Healthcare System,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Jumaa","sequence":"additional","affiliation":[{"name":"Center for Biological Signaling Studies BIOSS,Albert\u2010Ludwigs Universit\u00e4t,Freiburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.G.","family":"Webster","sequence":"additional","affiliation":[{"name":"Medical Research Service,VA San Diego Healthcare System,San Diego,CA"},{"name":"Department of Medicine, Division of Endocrinology and Metabolism,University of California San Diego,La Jolla,CA"},{"name":"Moores Cancer Center,University of California San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2014,11,25]]},"reference":[{"key":"hep27380-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3322\/caac.20107","article-title":"Global cancer 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