E-TABM-68 - MicroRNA profiling of human papillary thyroid carcinoma and normal thyroid to assess the role of miRNA genes in papillary thyroid carcinoma
Released on 28 February 2005, last updated on 27 March 2012
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 miRNAs are transcriptionally up-regulated in PTC tumors compared with unaffected thyroid tissue. A set of 5 miRNAs including the 3 most upregulated ones (miRs 221, 222, 146) distinguished unequivocally between PTC and normal thyroid. Additionally, miR-221 was upregulated in unaffected thyroid tissue in several PTC patients, presumably an early event in carcinogenesis. Tumors in which the upregulation (11-19 fold) of miRs 221, 222 and 146 was strongest showed dramatic loss of KIT transcript and Kit protein. In five of 10 such cases this was associated with germline single nucleotide changes in the two recognition sequences in KIT for these miRNAs. We conclude that upregulation of several miRs and down regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their downregulation.
microRNA profiling by array, disease state
Stefano Volinia <email@example.com>, Albert de la Chapelle, Carlo M. Croce, Chang-gong Liu, George A. Calin, Huiling He, Kaarle Franssila, Krystian Jazdzewski, Rebecca Nagy, Richard T. Kloos, Sandya Liyanarachchi, Saul Suster, Wei Li
The role of microRNA genes in papillary thyroid carcinoma. He, Huiling; Jazdzewski, Krystian; Li, Wei; Liyanarachchi, Sandya; Nagy, Rebecca; Volinia, Stefano; Calin, George A.; Liu, Chang-gong; Franssila, Kaarle; Suster, Saul; Kloos, Richard T.; Croce, Carlo M.; de la Chapelle, Albert. Proc Natl Acad Sci U S A 102(52):19075 (2005), Europe PMC 16365291