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The role of microRNA genes in papillary thyroid carcinoma.


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.

SUBMITTER: He H 

PROVIDER: S-EPMC1323209 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature

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The role of microRNA genes in papillary thyroid carcinoma.

He Huiling H   Jazdzewski Krystian K   Li Wei W   Liyanarachchi Sandya S   Nagy Rebecca R   Volinia Stefano S   Calin George A GA   Liu Chang-Gong CG   Franssila Kaarle K   Suster Saul S   Kloos Richard T RT   Croce Carlo M CM   de la Chapelle Albert A  

Proceedings of the National Academy of Sciences of the United States of America 20051219 52


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 sev  ...[more]

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