{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:11:38Z","timestamp":1778875898827,"version":"3.51.4"},"reference-count":119,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:p>\n                    Germline and somatic changes in\n                    <jats:italic>DICER1<\/jats:italic>\n                    and\n                    <jats:italic>DGCR8<\/jats:italic>\n                    microprocessors confer risk of developing benign and malignant thyroid lesions, yet the molecular events driving malignant transformation remain unclear. We trace the molecular trajectories from benignity to malignancy in\n                    <jats:italic>DICER1-<\/jats:italic>\n                    and\n                    <jats:italic>DGCR8<\/jats:italic>\n                    -mutated thyroid lesions using multiomic profiling on over 30\n                    <jats:italic>DICER1-\/DGCR8<\/jats:italic>\n                    -mutated samples. Our findings reveal a progressive, specific, and linear accumulation of genetic changes, which when combined with enhanced downregulation of miRNAs distinguished\n                    <jats:italic>DICER1-\/DGCR8<\/jats:italic>\n                    -malignant lesions from their benign counterparts. Compensatory hypomethylation of miRNA-encoding genes characterized\n                    <jats:italic>DICER1-\/DGCR8<\/jats:italic>\n                    -benign lesions, but as the tumors progressed to malignancy, methylation was partly reimposed, reversing the attempts to activate miRNA-encoded genes and further compromising miRNA production. Transcriptomic analyses revealed mutation-specific effects on the microenvironment, whereby\n                    <jats:italic>DICER1<\/jats:italic>\n                    mutations activated canonical thyroid cancer progression pathways, whereas altered\n                    <jats:italic>DGCR8<\/jats:italic>\n                    associated with immune-related changes. This work unveils specific molecular events underlying malignant progression of miRNA-biogenesis-related thyroid tumors and identifies potential biomarkers and disease etiology mechanisms.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.198338","type":"journal-article","created":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T19:00:48Z","timestamp":1770577248000},"source":"Crossref","is-referenced-by-count":0,"title":["Tracing the molecular route to progression in miRNA-biogenesis-defective thyroid lesions"],"prefix":"10.1172","volume":"11","author":[{"given":"Anne-Sophie","family":"Chong","sequence":"first","affiliation":[{"name":"Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, Barcelona, Spain."},{"name":"Genetics Program, Faculty of Biology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Roca","sequence":"additional","affiliation":[{"name":"Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, Barcelona, Spain."},{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Morales-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Dorca","sequence":"additional","affiliation":[{"name":"Pathology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, Barcelona, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ver\u00f3nica","family":"Barea","sequence":"additional","affiliation":[{"name":"Genetics and Genomics, Faculty of Biology, University of Barcelona, Barcelona, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Ruz-Caracuel","sequence":"additional","affiliation":[{"name":"Ram\u00f3n y Cajal Health Research Institute (IRYCIS), Ram\u00f3n y Cajal University Hospital, CIBERONC, Madrid, Spain."},{"name":"Department of Pathology, Ram\u00f3n y Cajal University Hospital, Madrid, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Valderrabano","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, Madrid, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlota","family":"Rovira","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Sant Joan de D\u00e9u, University of Barcelona, Barcelona, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Jou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Sant Joan de D\u00e9u, University of Barcelona, Barcelona, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doroth\u00e9e","family":"Bouron-Dal Soglio","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte-Justine Research Center, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca D.","family":"Chernock","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, and"},{"name":"Department of Otolaryngology Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovana T.","family":"Torrezan","sequence":"additional","affiliation":[{"name":"Clinical and Functional Genomics Group, International Research Center\/CIPE, A.C. 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