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Endocrine-Related Cancer 13 (2) 497-508    DOI: 10.1677/erc.1.01209
Copyright © 2006 by the Society for Endocrinology.
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MicroRNA deregulation in human thyroid papillary carcinomas

P Pallante*,1,2, R Visone*,1,3, M Ferracin4, A Ferraro2, M T Berlingieri1, G Troncone2,5, G Chiappetta6, C G Liu3, M Santoro1,2, M Negrini4, C M Croce3 and A Fusco1,2

1 Dipartimento di Biologia e Patologia Cellulare e Molecolare, c/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli ‘Federico II’, via Pansini, 5, 80131 Naples, Italy
2 NOGEC (Naples Oncogenomic Center)-CEINGE, Biotecnologie Avanzate-Napoli and SEMM – European School of Molecular Medicine – Naples Site, via Comunale Margherita, 482, 80145 Naples, Italy
3 Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, 410 West 12th Avenue, Columbus, Ohio 43210, USA
4 Dipartimento di Medicina Sperimentale e Diagnostica, e Centro Interdipartimentale per la Ricerca sul Cancro, 44100 Ferrara, Italy
5 Dipartimento di Anatomia Patologica e Citopatologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli ‘Federico II’, via Pansini, 5, 80131 Naples, Italy
6 Istituto Nazionale dei Tumori, Fondazione Pascale, via Mariano Semmola, 80131 Naples, Italy

(Requests for offprints should be addressed to A Fusco; Email: afusco{at}napoli.com or C M Croce; Email: carlo.croce{at}osumc.edu)

MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in a wide range of basic processes such as cell proliferation, development, apoptosis and stress response. It has recently been found that they are also abnormally expressed in many types of human cancer. We analyzed the genome-wide miRNA expression profile in human thyroid papillary carcinomas (PTCs) using a microarray (miRNACHIP microarray) containing hundreds of human precursor and mature miRNA oligonucleotide probes. Using this approach, we found an aberrant miRNA expression profile that clearly differentiates PTCs from normal thyroid tissues. In particular, a significant increase in miRNA (miR)-221, -222 and -181b was detected in PTCs in comparison with normal thyroid tissue. These results were further confirmed by northern blot and quantitative RT-PCR analyses. Moreover, RT-PCR revealed miR-221, -222 and -181b overexpression in fine needle aspiration biopsies corresponding to thyroid nodules, which were eventually diagnosed as papillary carcinomas after surgery. Finally, miR-221, -222 and -181b overexpression was also demonstrated in transformed rat thyroid cell lines and in mouse models of thyroid carcinogenesis. Functional studies, performed by blocking miR-221 function and by overexpressing miR-221 in human PTC-derived cell lines, suggest a critical role of miR-221 overexpression in thyroid carcinogenesis. In conclusion, these data, taken together, indicate an miRNA signature associated with PTCs, and suggest miRNA deregulation as an important event in thyroid cell transformation.




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