Specific microRNAs are downregulated in human thyroid anaplastic carcinomas
Specific microRNAs are downregulated in human thyroid anaplastic carcinomas
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DOI：
10.1038/sj.onc.1210564
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发表时间：
2007-11-29
期刊：
影响因子：
8
通讯作者：
Fusco, A.
中科院分区：
文献类型：
--
作者：
Visone, R.;Pallante, P.;Fusco, A.
甲状腺癌包括具有不同临床表现的广谱肿瘤。一方面是隐匿性乳头状癌（PTC），生长缓慢，临床无症状，另一方面是快速生长的间变性癌（ATC），这是人类最致命的肿瘤之一。我们分析了microRNA (miR) pro。使用微阵列（miRNACHIP微阵列）比较ATC与正常甲状腺的差异。通过这种方法，我们发现了一个异常的miR表达。这明显区分了ATC与正常甲状腺组织和以往研究中分析的PTC。特别是，与正常甲状腺组织相比，ATC中miR-30d、miR-125b、miR-26a和miR-30a-5p显著降低。这些结果通过northern blots、定量逆转录- pcr分析和原位杂交进一步证实。在两种人类atc来源的细胞系中，这四种mir的过表达表明miR-125b和miR-26a下调在甲状腺癌发生中起关键作用，因为实现了细胞生长抑制。相反，在同一细胞中过表达miR-30d和miR-30a-5p后，未观察到对细胞生长的影响。总之，这些数据表明miR特征与ATC相关，并表明miR失调是甲状腺细胞转化的一个重要事件。
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) pro. le of ATC in comparison to the normal thyroid using a microarray (miRNACHIP microarray). By this approach, we found an aberrant miR expression pro. le 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.