miR-191 down-regulation plays a role in thyroid follicular tumors through CDK6 targeting.

Autor: Colamaio M; Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli Federico II, Napoli, Italy., Borbone E, Russo L, Bianco M, Federico A, Califano D, Chiappetta G, Pallante P, Troncone G, Battista S, Fusco A
Jazyk: angličtina
Zdroj: The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2011 Dec; Vol. 96 (12), pp. E1915-24. Date of Electronic Publication: 2011 Sep 28.
DOI: 10.1210/jc.2011-0408
Abstrakt: 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: MEDLINE