miR-191 Down-Regulation Plays a Role in Thyroid Follicular Tumors through CDK6 Targeting

Autor: Marianna Colamaio, Daniela Califano, Gennaro Chiappetta, Mimma Bianco, Eleonora Borbone, Pierlorenzo Pallante, Sabrina Battista, Alfredo Fusco, Lucia Russo, Giancarlo Troncone, Antonella Federico
Přispěvatelé: Colamaio, Marianna, Borbone, E., Russo, L., Bianco, Mimma, Federico, Antonella, Califano, D., Chiappetta, G., Pallante, Pierlorenzo, Troncone, Giancarlo, Battista, Sabrina, Fusco, Alfredo
Rok vydání: 2011
Předmět:
Zdroj: The Journal of clinical endocrinology and metabolism 96 (2011): E1915–E1924. doi:10.1210/jc.2011-0408
info:cnr-pdr/source/autori:Colamaio, Marianna; Borbone, Eleonora; Russo, Lucia; Bianco, Mimma; Federico, Antonella; Califano, Daniela; Chiappetta, Gennaro; Pallante, Pierlorenzo; Troncone, Giancarlo; Battista, Sabrina; Fusco, Alfredo/titolo:miR-191 Down-Regulation Plays a Role in Thyroid Follicular Tumors through CDK6 Targeting/doi:10.1210%2Fjc.2011-0408/rivista:The Journal of clinical endocrinology and metabolism/anno:2011/pagina_da:E1915/pagina_a:E1924/intervallo_pagine:E1915–E1924/volume:96
DOI: 10.1210/jc.2011-0408
Popis: CONTEXT: Well-differentiated thyroid carcinomas include papillary (PTC) and follicular (FTC) carcinomas. FTC is usually a more aggressive form of cancer than the more common papillary type. miR-191 expression is frequently altered in several neoplasias, being up-regulated in some cases, such as pancreatic carcinomas, and down-regulated in other carcinomas, such as melanomas. OBJECTIVE: The objective was to evaluate the expression and the role of miR-191 in thyroid carcinogenesis. DESIGN: The expression of miR-191 was analyzed in tissues from patients with follicular adenoma (n = 24), FTC (n = 24), PTC (n = 15), anaplastic thyroid carcinoma (n = 8), and the follicular variant of PTC (n = 6) compared with normal thyroid tissues by quantitative RT-PCR. miR-191 expression was restored in the follicular thyroid cell line WRO, and the effects on cell proliferation, migration, and target expression were evaluated. RESULTS: miR-191 is down-regulated in follicular adenoma, FTC, and follicular variant of PTC. We identified CDK6, a serine-threonine kinase involved in the control of cell cycle progression, as a novel target of miR-191. Restoration of miR-191 expression in WRO cells reduces cell growth and migration rate on vitronectin. CDK6 overexpression, correlated with miR-191 down-regulation, was found in follicular adenoma and FTC, suggesting a role of miR-191 down-regulation in the generation of these neoplasias. CONCLUSIONS: Our results suggest that miR-191 down-regulation plays a role in thyroid neoplasias of the follicular histotype, likely by targeting CDK6.
Databáze: OpenAIRE