{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T09:26:15Z","timestamp":1793697975238,"version":"4.5.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["B83C22002870006"],"award-info":[{"award-number":["B83C22002870006"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"publisher","award":["RG1181642D25A6AF"],"award-info":[{"award-number":["RG1181642D25A6AF"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor originating from calcitonin producing C\u2010cells and accounts for 1\u20135% of thyroid cancers. Total thyroidectomy is curative in localized disease (N0), whereas lymph node metastases (N1) are associated with poorer prognosis. However, the molecular mechanisms driving the metastatic shift remain poorly understood. This study aimed to identify miRNA features linked to metastatic spread in MTC, focusing on the transition from N0 to N1. Co\u2010expression networks were constructed for N0 and N1 tumors, and differential connectivity analysis was used to identify key miRNAs acting as regulatory hubs. Functional annotation of their target genes was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome pathway analyses. Validation experiments were carried out in MTC cells to evaluate the effects of selected miRNAs on cell proliferation, survival, and MAPK pathway activation. Network analysis revealed distinct miRNA co\u2010expression patterns between N0 and N1 tumors. Differential network analysis highlighted\n                    <jats:italic>miR\u2010145\u20103p<\/jats:italic>\n                    as a central regulatory hub, exhibiting 29 altered co\u2010expression changes and a marked loss of connectivity in N1. Target enrichment identified 59 validated genes, including key oncogenic drivers such as\n                    <jats:italic>MYC<\/jats:italic>\n                    ,\n                    <jats:italic>PTEN<\/jats:italic>\n                    ,\n                    <jats:italic>BCL2<\/jats:italic>\n                    ,\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    ,\n                    <jats:italic>AKT1<\/jats:italic>\n                    , and\n                    <jats:italic>MAPK7<\/jats:italic>\n                    . In MTC cells, simultaneous inhibition of\n                    <jats:italic>miR\u2010145\u20103p<\/jats:italic>\n                    together with its top co\u2010expressed miRNAs increased proliferation and survival, and enhanced ERK phosphorylation, indicating MAPK pathway activation and a shift toward a more aggressive phenotype. In conclusion, this study identifies a miRNA regulatory hub centered on\n                    <jats:italic>miR\u2010145\u20103p<\/jats:italic>\n                    that is associated with metastatic progression and highlights the value of network\u2010based approaches in uncovering mechanisms of cancer dissemination. \u00a9 2026 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70116","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:37:47Z","timestamp":1788946667000},"page":"468-480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network based approach identifies\n                    <scp>\n                      <i>miR<\/i>\n                    <\/scp>\n                    <i>\u2010145\u20103p<\/i>\n                    as a central regulatory hub associated to the progression from localized to metastatic medullary thyroid carcinoma"],"prefix":"10.1002","volume":"270","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1290-4990","authenticated-orcid":false,"given":"Anna","family":"Citarella","sequence":"first","affiliation":[{"name":"Department of Life Science, Health, and Health Professions Link Campus University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0149-161X","authenticated-orcid":false,"given":"Manuela","family":"Petti","sequence":"additional","affiliation":[{"name":"Department of Computer, Control and Management Engineering Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0317-9854","authenticated-orcid":false,"given":"Zein Mersini","family":"Besharat","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7296-8112","authenticated-orcid":false,"given":"Caterina","family":"Alfano","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Splendiani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Trocchianesi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome  Rome 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