The role of microRNA genes in papillary thyroid carcinoma.
Proc Natl Acad Sci U S A, 2005/12/27;102(52):19075-80.
He H[1], Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM, de la Chapelle A
Affiliations
PMID: 16365291
Impact factor: 12.779
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.
MeSH terms
Base Sequence; Blotting, Northern; Blotting, Western; Carcinoma, Papillary; Computational Biology; DNA; Down-Regulation; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Models, Statistical; Molecular Sequence Data; Mutation; Neoplasms; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis; Polymorphism, Genetic; Proto-Oncogene Proteins c-kit; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Software; Thyroid Gland; Thyroid Neoplasms; Up-Regulation
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