Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli Federico II, Centro Ingegneria Genetica and European School of Molecular Medicine, 80131 Naples, Italy.
J Clin Endocrinol Metab. 2011 Sep;96(9):E1388-98. doi: 10.1210/jc.2011-0345. Epub 2011 Jul 13.
Micro-RNA have emerged as an important class of short endogenous RNA that act as posttranscriptional regulators of gene expression and are constantly deregulated in human cancer. MiR-1 has been found down-regulated in lung, colon, and prostate cancer.
In this study, we investigated the possible role of miR-1 in thyroid carcinogenesis.
We have analyzed miR-1 expression in a panel of thyroid neoplasias including benign and malignant lesions and searched for miR-1 targets.
Our results show that miR-1 expression is drastically down-regulated in thyroid adenomas and carcinomas in comparison with normal thyroid tissue. Interestingly, miR-1 down-regulation was also found in thyroid hyperproliferative nonneoplastic lesions such as goiters. We identified the CCND2, coding for the cyclin D2 (CCND2) protein that favors the G1/S transition, CXCR4, and SDF-1α genes, coding for the receptor for the stromal cell derived factor-1 (SDF-1)/CXCL12 chemokine and its ligand SDF-1/CXCL12, respectively, as miR-1 targets. An inverse correlation was found between miR-1 expression and CXC chemokine receptor 4 (CXCR4) and SDF-1α protein levels in papillary and anaplastic thyroid carcinomas. Consistent with a role of the CCND2 protein in cell proliferation and CXCR4 and SDF-1α proteins in cell invasion and metastasis, functional studies demonstrate that miR-1 is able to inhibit thyroid carcinoma cell proliferation and migration.
These results indicate the involvement of miR-1 in thyroid cell proliferation and migration, validating a role of miR-1 down-regulation in thyroid carcinogenesis.
微 RNA 已成为一类重要的短内源性 RNA，作为基因表达的转录后调节剂，在人类癌症中不断失调。MiR-1 已在肺癌、结肠癌和前列腺癌中发现下调。
本研究旨在探讨 miR-1 在甲状腺癌发生中的可能作用。
我们分析了包括良性和恶性病变在内的一组甲状腺肿瘤中 miR-1 的表达，并寻找 miR-1 的靶标。
我们的结果表明，与正常甲状腺组织相比，miR-1 在甲状腺腺瘤和癌中表达明显下调。有趣的是，miR-1 的下调也在甲状腺过度增生的非肿瘤病变中发现，如甲状腺肿。我们鉴定了编码细胞周期蛋白 D2（CCND2）蛋白的 CCND2 基因，该蛋白促进 G1/S 期过渡，以及编码基质细胞衍生因子-1（SDF-1）/CXCL12 趋化因子受体和其配体 SDF-1/CXCL12 的 CXCR4 基因，分别作为 miR-1 的靶标。在甲状腺乳头状癌和间变性甲状腺癌中，发现 miR-1 表达与 CXCR4 和 SDF-1α 蛋白水平呈负相关。与 CCND2 蛋白在细胞增殖中的作用以及 CXCR4 和 SDF-1α 蛋白在细胞侵袭和转移中的作用一致，功能研究表明 miR-1 能够抑制甲状腺癌细胞的增殖和迁移。
这些结果表明 miR-1 参与了甲状腺细胞的增殖和迁移，验证了 miR-1 下调在甲状腺癌发生中的作用。
