The role of microRNA genes in papillary thyroid carcinoma
The role of microRNA genes in papillary thyroid carcinoma
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DOI：
10.1073/pnas.0509603102
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发表时间：
2005-12-27
影响因子：
11.1
通讯作者：
de la Chapelle, A
中科院分区：
文献类型：
--
作者：
He, HL;Jazdzewski, K;de la Chapelle, A
除了RET/PTC-RAS-BRAF通路的改变外，对甲状腺乳头状癌（PTC）的遗传学知之甚少。我们发现，与未受影响的甲状腺组织相比，PTC肿瘤中的许多microRNAs（miRNAs）在转录上上调。一组五种miRNAs，包括三种上调最多的miRNAs（miR-221，-222和-146），明确区分了PTC和正常甲状腺。此外，miR-221在几个PTC患者未受影响的甲状腺组织中上调，推测是癌发生的早期事件。其中miR-221、-222和-146的上调（11至19倍）最强的肿瘤显示KIT转录物和Kit蛋白的显著损失。在10例此类病例中的5例中，这种表达下调与这些miRNA的KIT中的两个识别序列中的种系单核苷酸变化有关。我们的结论是，上调的几个miRs和调控的KIT参与PTC的发病机制，和序列的变化，靶基因的miRNAs可以有助于他们的调节。
Apart from alterations in the RET/PTC-RAS-BRAF pathway, comparatively little is known about the genetics of papillary thyroid carcinoma (PTC). We show that numerous microRNAs (miRNAs) are transcriptionally up-regulated in PTC tumors compared with unaffected thyroid tissue. A set of five miRNAs, including the three most up-regulated ones (miR-221, -222, and -146), distinguished unequivocally between PTC and normal thyroid. Additionally, miR-221 was up-regulated in unaffected thyroid tissue in several PTC patients, presumably an early event in carcinogenesis. Tumors in which the up-regulation (11- to 19-fold) of miR-221, -222, and -146 was strongest showed dramatic loss of KIT transcript and Kit protein. In 5 of 10 such cases, this down expression was associated with germline single-nucleotide changes in the two recognition sequences in KIT for these miRNAs. We conclude that up-regulation of several miRs and regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their regulation.