{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:42:25Z","timestamp":1788910945561,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T00:00:00Z","timestamp":1566950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["AIO15152858"],"award-info":[{"award-number":["AIO15152858"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,1,15]]},"abstract":"<jats:p>It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow\u2010up of 96\u2009months. MiRNome profiles correlated with tumor\u2010specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differential expression analysis revealed a consistent hsa\u2010miR\u2010139\u20105p downexpression in primary carcinomas from patients with recurrent\/metastatic disease compared to disease\u2010free patients, sustained in paired local metastases and validated in publicly available thyroid cancer series. Exogenous expression of hsa\u2010miR\u2010139\u20105p significantly reduced migration and proliferation of anaplastic thyroid cancer cells. Proteomic analysis indicated RICTOR, SMAD2\/3 and HNRNPF as putative hsa\u2010miR\u2010139\u20105p targets in our cell system. Abundance of <jats:italic>HNRNPF<\/jats:italic> mRNA, encoding an alternative splicing factor involved in cryptic exon inclusion\/exclusion, inversely correlated with hsa\u2010miR\u2010139\u20105p expression in human tumors. RNA sequencing analysis revealed 174 splicing events differentially regulated upon HNRNPF repression in our cell system, affecting genes involved in RTK\/RAS\/MAPK and PI3K\/AKT\/MTOR signaling cascades among others. These results point at the hsa\u2010miR\u2010139\u20105p\/HNRNPF axis as a novel regulatory mechanism associated with the modulation of major thyroid cancer signaling pathways and tumor virulence.<\/jats:p>","DOI":"10.1002\/ijc.32622","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T09:55:24Z","timestamp":1565603724000},"page":"521-530","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Hsa\u2010miR\u2010139\u20105p is a prognostic thyroid cancer marker involved in HNRNPF\u2010mediated alternative splicing"],"prefix":"10.1002","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4452-4469","authenticated-orcid":false,"given":"Cristina","family":"Montero\u2010Conde","sequence":"first","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osvaldo","family":"Gra\u00f1a\u2010Castro","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Mart\u00edn\u2010Serrano","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel M.","family":"Mart\u00ednez\u2010Montes","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Zarzuela","sequence":"additional","affiliation":[{"name":"Proteomics Core Unit and Proteored\u2010ISCIII Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Proteomics Core Unit and Proteored\u2010ISCIII Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Torres\u2010Perez","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Pita","sequence":"additional","affiliation":[{"name":"CEGEN Unit Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Cordero\u2010Barreal","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis J.","family":"Leandro\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Let\u00f3n","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"L\u00f3pez de Silanes","sequence":"additional","affiliation":[{"name":"Telomeres and Telomerase Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonsoles","family":"Guadalix","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"P\u00e9rez\u2010Barrios","sequence":"additional","affiliation":[{"name":"Anatomical Pathology Section Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almudena","family":"Guerrero\u2010\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"\u00c1lvarez\u2010Escol\u00e1","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita M.","family":"Regojo\u2010Zapata","sequence":"additional","affiliation":[{"name":"Anatomical Pathology Section Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Calsina","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Remacha","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5651-4313","authenticated-orcid":false,"given":"Juan M.","family":"Rold\u00e1n\u2010Romero","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Santos","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Lanillos","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Jord\u00e1","sequence":"additional","affiliation":[{"name":"Program for Predictive and Personalized Medicine of Cancer Germans Trias i Pujol Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garcilaso","family":"Riesco\u2010Eizaguirre","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department Hospital Universitario de M\u00f3stoles  Madrid Spain"},{"name":"Biomedical Research Networking Centre in Oncology (CIBERONC) Institute of Health Carlos III  Madrid Spain"},{"name":"Universidad Francisco de Vitoria  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carles","family":"Zafon","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit and Endocrinology Department Hospital Universitari Vall d'Hebron  Barcelona Spain"},{"name":"Biomedical Research Networking Centre on Diabetes and Associated Metabolic Diseases (CIBERDEM) Institute of Health Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gonz\u00e1lez\u2010Neira","sequence":"additional","affiliation":[{"name":"CEGEN Unit Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Blasco","sequence":"additional","affiliation":[{"name":"Telomeres and Telomerase Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1tima","family":"Al\u2010Shahrour","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8750-7338","authenticated-orcid":false,"given":"Cristina","family":"Rodr\u00edguez\u2010Antona","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Casc\u00f3n","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Robledo","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group Spanish National Cancer Research Centre (CNIO)  Madrid Spain"},{"name":"Biomedical Research Networking Centre on Rare Diseases (CIBERER) Institute of Health Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2011.0535"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-08-0154"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2383"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0373"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46382"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209288"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.050"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2015.44"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-13-0266"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.246"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08225-3"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30277-7"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-015-9724-3"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-015-9363-x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.229831"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-3348"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-17-0334"},{"key":"e_1_2_7_19_1","first-page":"7799","article-title":"MicroRNA\u2010139 targets fibronectin 1 to inhibit papillary thyroid carcinoma progression","volume":"14","author":"Ye Y","year":"2017","journal-title":"Oncol Lett"},{"key":"e_1_2_7_20_1","first-page":"7153","article-title":"Integrated microRNA\u2010mRNA analyses of distinct expression profiles in follicular thyroid tumors","volume":"14","author":"Chi J","year":"2017","journal-title":"Oncol Lett"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26445"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2013.05.008"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.042143.113"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M400129-MCP200"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91144"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-3125"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1802415115"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.44"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1248"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0024"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1248"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.02.001"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.305862.117"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.01.088"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.242214.118"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1183"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.07.001"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.11.010"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32622","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.32622","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32622","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T09:50:05Z","timestamp":1694253005000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.32622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,28]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,1,15]]}},"alternative-id":["10.1002\/ijc.32622"],"URL":"https:\/\/doi.org\/10.1002\/ijc.32622","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,28]]},"assertion":[{"value":"2019-03-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}