title: 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.
authors.affiliation: Human Cancer Genetics Program, Department of Pathology, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Huiling
authors.initials: H
authors.lastname: He
authors.forename: Krystian
authors.initials: K
authors.lastname: Jazdzewski
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Sandya
authors.initials: S
authors.lastname: Liyanarachchi
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nagy
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Kaarle
authors.initials: K
authors.lastname: Franssila
authors.forename: Saul
authors.initials: S
authors.lastname: Suster
authors.forename: Richard T
authors.initials: RT
authors.lastname: Kloos
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Albert
authors.initials: A
authors.lastname: de la Chapelle
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry; D015233:Models, Statistical; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012984:Software; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000628:therapy; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit