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

摘要

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.