Down-Regulation of the miR-25 and miR-30d Contributes to the Development of Anaplastic Thyroid Carcinoma Targeting the Polycomb Protein EZH2
Down-Regulation of the miR-25 and miR-30d Contributes to the Development of Anaplastic Thyroid Carcinoma Targeting the Polycomb Protein EZH2
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DOI：
10.1210/jc.2011-3068
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发表时间：
2012-05-01
影响因子：
5.8
通讯作者：
Fusco, Alfredo
中科院分区：
文献类型：
--
作者：
Esposito, Francesco;Tornincasa, Mara;Fusco, Alfredo
内容：我们之前已经证明，一组micro-RNA（miRNA）在未分化甲状腺癌中相对于正常甲状腺组织和分化型甲状腺癌显著下调。目的：目的是评估其中两种下调的miRNA，miR-25和miR-30 d在甲状腺癌发生中的作用。设计：miR-25和miR-30 d在ACT-1、8505 c和FRO未分化甲状腺细胞系中的表达得以恢复，并评估了它们对细胞增殖、迁移和靶点表达的影响。我们报告了miR-25和miR-30 d靶向具有致癌活性的polycomb蛋白增强子zeste 2（EZH 2），该蛋白在未分化甲状腺癌中显著上调，但在分化型甲状腺癌中则没有。miR-25和miR-30 d的异位表达通过诱导G2/M期细胞周期阻滞抑制甲状腺未分化癌细胞的增殖和集落形成。结论：miR-25和miR-30 d的下调可能参与甲状腺癌的发生发展过程，从而导致以EZH 2 mRNA为靶点的未分化癌的发生发展。（临床内分泌代谢杂志97：E710-E718，2012）
Context: We have previously demonstrated that a set of micro-RNA (miRNA) is significantly down-regulated in anaplastic thyroid carcinomas with respect to normal thyroid tissues and to differentiated thyroid carcinomas.Objective: The objective was to evaluate the role of two of these down-regulated miRNA, miR-25 and miR-30d, in thyroid carcinogenesis.Design: miR-25 and miR-30d expression was restored in the ACT-1, 8505c, and FRO anaplastic thyroid cell lines, and their effects on cell proliferation, migration, and target expression were evaluated.Results: We report that miR-25 and miR-30d target the polycomb protein enhancer of zeste 2 (EZH2) that has oncogenic activity and is drastically up-regulated in anaplastic thyroid carcinomas but not in the differentiated ones. Ectopic expression of miR-25 and miR-30d inhibited proliferation and colony formation of anaplastic thyroid carcinoma cells by inducing G2/M-phase cell-cycle arrest. Finally, we found an inverse correlation between the expression of these miRNA and the EZH2 protein levels in anaplastic thyroid carcinomas, suggesting a critical role of these miRNA in regulating EZH2 expression also in vivo.Conclusion: The down-regulation of miR-25 and miR-30d could contribute to the process of thyroid cancer progression, leading to the development of anaplastic carcinomas targeting EZH2 mRNA. (J Clin Endocrinol Metab 97: E710-E718, 2012)