| Literature DB >> 16365291 |
Huiling He1, Krystian Jazdzewski, Wei Li, Sandya Liyanarachchi, Rebecca Nagy, Stefano Volinia, George A Calin, Chang-Gong Liu, Kaarle Franssila, Saul Suster, Richard T Kloos, Carlo M Croce, Albert de la Chapelle.
Abstract
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.Entities:
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Year: 2005 PMID： 16365291 PMCID： PMC1323209 DOI： 10.1073/pnas.0509603102
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205