The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci U S A 2005 Dec 27;102(52):19075-80
Date
12/21/2005Pubmed ID
16365291Pubmed Central ID
PMC1323209DOI
10.1073/pnas.0509603102Scopus ID
2-s2.0-30044436911 (requires institutional sign-in at Scopus site) 1110 CitationsAbstract
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.
Author List
He H, 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 AMESH terms used to index this publication - Major topics in bold
Base SequenceBlotting, 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
