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.
J Clin Endocrinol Metab. 2011 Dec;96(12):E1915-24. doi: 10.1210/jc.2011-0408. Epub 2011 Sep 28.
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.
The objective was to evaluate the expression and the role of miR-191 in thyroid carcinogenesis.
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.
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.
Our results suggest that miR-191 down-regulation plays a role in thyroid neoplasias of the follicular histotype, likely by targeting CDK6.
分化型甲状腺癌包括乳头状癌（PTC）和滤泡状癌（FTC）。FTC 通常比更为常见的乳头状癌具有更强的侵袭性。miR-191 的表达在多种肿瘤中经常发生改变，在某些情况下上调，如胰腺癌，而在其他癌中下调，如黑色素瘤。
目的是评估 miR-191 在甲状腺癌发生中的表达和作用。
通过定量 RT-PCR 分析 24 例滤泡性腺瘤、24 例 FTC、15 例 PTC、8 例间变性甲状腺癌和 6 例 PTC 的滤泡变体患者组织与正常甲状腺组织中 miR-191 的表达。在滤泡状甲状腺细胞系 WRO 中恢复 miR-191 的表达，并评估其对细胞增殖、迁移和靶基因表达的影响。
miR-191 在滤泡性腺瘤、FTC 和 PTC 的滤泡变体中下调。我们鉴定出 CDK6，一种参与细胞周期进程控制的丝氨酸-苏氨酸激酶，是 miR-191 的一个新靶基因。在 WRO 细胞中恢复 miR-191 的表达会降低细胞在 vitronectin 上的生长和迁移率。在滤泡性腺瘤和 FTC 中发现 CDK6 的过表达与 miR-191 的下调相关，提示 miR-191 的下调在这些肿瘤的发生中起作用。
我们的结果表明，miR-191 的下调可能通过靶向 CDK6 在滤泡状甲状腺肿瘤中发挥作用。
