MicroRNA deregulation in human thyroid papillary carcinomas

作者：Pierlorenzo Pallante, Rosa Visone, Manuela Ferracin, Angelo Ferraro, Maria Teresa Berlingieri, Giancarlo Troncone, Gennaro Chiappetta, Caigang Liu, Massimo Mattia Santoro, Massimo Negrini, Carlo Maria Croce, Alfredo Fusco · 发表于：Endocrine Related Cancer · 年份：2006 · DOI：10.1677/erc.1.01209 · 被引用次数：530 · 研究领域：MicroRNA in disease regulation、Cancer-related molecular mechanisms research、RNA modifications and cancer

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 s...