MiR-1 is a tumor suppressor in thyroid carcinogenesis targeting CCND2, CXCR4, and SDF-1alpha

• Published in: The journal of clinical endocrinology and metabolism 2011-09, Vol.96 (9), p.E1388-E1398
• Main Authors: Leone, Vincenza, D'Angelo, Daniela, Rubio, Ileana, de Freitas, Paula Mussnich, Federico, Antonella, Colamaio, Marianna, Pallante, Pierlorenzo, Medeiros-Neto, Geraldo, Fusco, Alfredo
• Format: Article
• Language: English
• Subjects: Adenoma - genetics; Adenoma - metabolism; Animals; Carcinoma - genetics; Carcinoma - metabolism; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation; Chemokine CXCL12 - genetics; Chemokine CXCL12 - metabolism; Cyclin D2 - genetics; Cyclin D2 - metabolism; Down-Regulation; Humans; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Receptors, CXCR4 - genetics; Receptors, CXCR4 - metabolism; Signal Transduction - genetics; Thyroid Gland - metabolism; Thyroid Neoplasms - genetics; Thyroid Neoplasms - metabolism
• ISSN: 1945-7197
• DOI: 10.1210/jc.2011-0345

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.