{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:32:40Z","timestamp":1783632760040,"version":"3.55.0"},"reference-count":46,"publisher":"Bioscientifica","issue":"5","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The genetic component is thought to play an important role in the development of familial non-medullary thyroid carcinoma (fNMTC), but the involved molecular mechanisms and genes are poorly understood. The MAPK kinase cascade, particularly involving RAS and BRAF, is crucial in cancer development, with RIN1 emerging as a notable gene due to its differential expression across various tumor types. We identified a frameshift mutation (c.798delC: p.V267Sfs*83) in the RIN1 gene in a family with non-medullary thyroid cancer (NMTC) through whole-exome sequencing. Paraffin-embedded tumor tissues were analyzed to investigate the mutation\u2019s characteristics and its potential implications within the thyroid cellular context. Functional assays and RNA sequencing using CRISPR\/Cas9-edited Nthy-ori 3-1 thyroid cell line and xenograft zebrafish models confirmed the mutation effect and the putative RIN1 tumor suppressor role. The study revealed significant alterations in cellular behavior upon RIN1 knockout, including increased cell viability, proliferation and colony formation, alongside morphological changes indicative of epithelial\u2013mesenchymal transition. Enhanced phosphorylation of ERK and AKT suggested MAPK pathway dysregulation following RIN1 depletion, supporting its potential tumor suppressive role. Phenotypic rescue experiments confirmed that reintroduction of wild-type RIN1 restored normal cellular behavior. RNA sequencing demonstrated differential gene expression between RIN1\u2212\/\u2212 and control cells, particularly affecting pathways associated with cancer progression, closely resembled signatures specific to NMTC. This study provides compelling evidence supporting RIN1 as a tumor suppressor gene within thyroid cells. In addition, the findings highlight its potential significance as novel gene involved in FNMTC pathogenesis.<\/jats:p>","DOI":"10.1530\/erc-24-0344","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T11:36:20Z","timestamp":1742556980000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the tumor suppressor role of\n                    <i>RIN1<\/i>\n                    in familial thyroid carcinoma"],"prefix":"10.1530","volume":"32","author":[{"given":"Luna","family":"Picello","sequence":"first","affiliation":[{"name":"Department of Biology, University of Padova 1 , ,","place":["Padova, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Dalle Nogare","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova 1 , ,","place":["Padova, 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Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Carra","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano 4 , ,","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Oldani","sequence":"additional","affiliation":[{"name":"Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano 3 , ,","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Gentilini","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia 5 , ,","place":["Pavia, Italy"]},{"name":"Bioinformatics and Statistical Genomics Unit, IRCCS Istituto Auxologico Italiano 6 , ,","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0716-481X","authenticated-orcid":true,"given":"Laura","family":"Fugazzola","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS 7 , ,","place":["Milan, Italy"]},{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano 8 , ,","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antongiulio","family":"Faggiano","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Clinical and Molecular Medicine, European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Sant'Andrea Hospital, Sapienza University of Rome 9 , ,","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2478-683X","authenticated-orcid":true,"given":"Giovanni","family":"Vitale","sequence":"additional","affiliation":[{"name":"Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano 3 , ,","place":["Milan, Italy"]},{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan 10 , ,","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4065-4677","authenticated-orcid":true,"given":"Gianluca","family":"Occhi","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova 1 , ,","place":["Padova, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Vazza","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova 1 , ,","place":["Padova, 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