1. ¹Dipartimento 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', Naples, Italy
2. ²NOGEC (Naples Oncogenomic Center)-CEINGE, Biotecnologie Avanzate-Napoli, & SEMM - European School of Molecular Medicine – Naples Site, Naples, Italy
3. ³Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA
4. ⁴Dipartimento di Istopatologia, Ospedale Sant'Andrea, Università di Roma 'La Sapienza', Rome, Italy
5. ⁵Dipartimento di Medicina Sperimentale e Diagnostica, Centro Interdipartimentale per la Ricerca sul Cancro, Università di Ferrara, Ferrara, Italy
6. ⁶Dipartimento di Anatomia Patologica e Citopatologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli 'Federico II', Naples, Italy
7. ⁷Dipartimento di Patologia, Università di Verona, Verona, Italy
8. ⁸Dipartimento di Patologia, Università di Bologna – Ospedale Bellaria, Bologna, Italy

Correspondence: Professor A Fusco, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli 'Federico II', via Pansini 5, 80131 Napoli-Italy. E-mail: afusco@napoli.com; CM Croce, Division of Human Cancer Genetics, Ohio State University, 410 West 12th Avenue, Columbus, OH 43210, USA. E-mail: carlo.croce@osumc.edu

⁹These two authors contributed equally to this work.

Received 26 January 2007; Revised 24 April 2007; Accepted 3 May 2007; Published online 11 June 2007.

Abstract

Thyroid carcinomas comprise a broad spectrum of tumors with different clinical behaviors. On the one side, there are occult papillary carcinomas (PTC), slow growing and clinically silent, and on the other side, rapidly growing anaplastic carcinomas (ATC), which are among the most lethal human neoplasms. We have analysed the microRNA (miR) profile of ATC in comparison to the normal thyroid using a microarray (miRNACHIP microarray). By this approach, we found an aberrant miR expression profile that clearly differentiates ATC from normal thyroid tissues and from PTC analysed in previous studies. In particular, a significant decrease in miR-30d, miR-125b, miR-26a and miR-30a-5p was detected in ATC in comparison to normal thyroid tissue. These results were further confirmed by northern blots, quantitative reverse transcription–PCR analyses and in situ hybridization. The overexpression of these four miRs in two human ATC-derived cell lines suggests a critical role of miR-125b and miR-26a downregulation in thyroid carcinogenesis, since a cell growth inhibition was achieved. Conversely, no effect on cell growth was observed after the overexpression of miR-30d and miR-30a-5p in the same cells. In conclusion, these data indicate a miR signature associated with ATC and suggest the miR deregulation as an important event in thyroid cell transformation.