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Mario Monaco Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale', IRCCS, Italy

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Gennaro Chiappetta Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale', IRCCS, Italy

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Concetta Aiello Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale', IRCCS, Italy

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Antonella Federico Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), Consiglio Nazionale delle Ricerche (CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli ‘Federico II', Naples, Italy

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Romina Sepe Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), Consiglio Nazionale delle Ricerche (CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli ‘Federico II', Naples, Italy

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Daniela Russo Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale', IRCCS, Italy

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Alfredo Fusco Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), Consiglio Nazionale delle Ricerche (CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli ‘Federico II', Naples, Italy
Instituto Nacional de Câncer - INCA, Rio de Janeiro, Brazil

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Pierlorenzo Pallante Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), Consiglio Nazionale delle Ricerche (CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli ‘Federico II', Naples, Italy

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Background: Previous analysis of CBX7 expression in a large number of thyroid adenoma and carcinoma samples revealed a progressive reduction of CBX7 levels that was well related with the malignant grade of thyroid neoplasias. Hürthle cell tumors are unusual thyroid neoplasms characterized by the presence of particular cells called oncocytes. Objectives: In order to develop new tools for a more accurate diagnosis of Hürthle cell tumors of the thyroid, we evaluated CBX7 protein levels to verify the possible presence of an expression signature. Methods: CBX7 expression was evaluated by immunohistochemistry in a panel of thyroid tissue sections including normal thyroids, goiters, follicular adenomas and oncocytic lesions. Results: CBX7 expression was low or null in 68% of Hürthle adenomas, whereas it was comparable to normal thyroid tissue in Hürthle hyperplasias and follicular adenomas. Conclusions: Reduced expression of CBX7 suggests a more aggressive identity of Hürthle adenomas with respect to non-Hürthle ones.

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Vincenza Leone Istituto di Endocrinologia ed Oncologia Sperimentale-CNR, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II', Naples, Italy

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Concetta Langella Istituto di Endocrinologia ed Oncologia Sperimentale-CNR, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II', Naples, Italy

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Francesco Esposito Istituto di Endocrinologia ed Oncologia Sperimentale-CNR, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II', Naples, Italy

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Marco De Martino Istituto di Endocrinologia ed Oncologia Sperimentale-CNR, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II', Naples, Italy

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Myriam Decaussin-Petrucci Department of Pathology, Lyon Sud Hospital Center, Hospices Civils de Lyon, Lyon, France

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Gennaro Chiappetta Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale', IRCCS, Naples, Italy

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Antonio Bianco Dipartimento di Sanità Pubblica, Università di Napoli Federico II, Naples, Italy

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Alfredo Fusco Istituto di Endocrinologia ed Oncologia Sperimentale-CNR, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II', Naples, Italy
Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil

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We have previously studied the function of microRNAs (miRNAs) in thyroid cells using the differentiated rat thyroid PC Cl 3 cells that need thyrotropin (TSH) for their growth. The miRNA expression profile examination allowed the detection of a set of miRNAs downregulated and upregulated by TSH. Here, we first demonstrated that upregulation of miR-130b-3p occurs through a protein kinase A-cAMP-responsive element binding protein (CREB)-dependent mechanism. Then, we analyzed its expression in human thyroid follicular adenomas, where a constitutive CREB activation is frequently present. miR-130b-3p results in upregulation with a high fold-change in most thyroid follicular adenomas. Then, we identified CCDC6, coding for a protein that interacts with CREB1 leading to the transcriptional repression of CREB1 target genes, as a target of this miRNA. The targeting of CCDC6 by miR-130b-3p likely accounts for the mechanism by which its upregulation contributes to the development of thyroid adenomas increasing CREB1 activity.

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