Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri M T, Troncone G, Chiappetta G, Liu C G, Santoro M, Negrini M, Croce C M, Fusco A
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.
Endocr Relat Cancer. 2006 Jun;13(2):497-508. doi: 10.1677/erc.1.01209.
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.
微小RNA（miRNA）是一类小的非编码RNA，参与细胞增殖、发育、凋亡和应激反应等广泛的基本过程。最近发现它们在多种人类癌症中也异常表达。我们使用包含数百种人类前体和成熟miRNA寡核苷酸探针的微阵列（miRNACHIP微阵列）分析了人类甲状腺乳头状癌（PTC）的全基因组miRNA表达谱。通过这种方法，我们发现了一种异常的miRNA表达谱，可将PTC与正常甲状腺组织清楚地区分开来。特别是，与正常甲状腺组织相比，在PTC中检测到miRNA（miR）-221、-222和-181b显著增加。这些结果通过Northern印迹和定量RT-PCR分析得到进一步证实。此外，RT-PCR显示在对应于甲状腺结节的细针穿刺活检中miR-221、-222和-181b过表达，这些结节在手术后最终被诊断为乳头状癌。最后，在转化的大鼠甲状腺细胞系和甲状腺癌发生的小鼠模型中也证实了miR-221、-222和-181b过表达。通过在人PTC来源的细胞系中阻断miR-221功能和过表达miR-221进行的功能研究表明，miR-221过表达在甲状腺癌发生中起关键作用。总之，这些数据综合表明与PTC相关的miRNA特征，并提示miRNA失调是甲状腺细胞转化中的一个重要事件。
