title: MiR-1 is a tumor suppressor in thyroid carcinogenesis targeting CCND2, CXCR4, and SDF-1alpha.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  In this study, we investigated the possible role of miR-1 in thyroid carcinogenesis.
  
  
  METHODS
  We have analyzed miR-1 expression in a panel of thyroid neoplasias including benign and malignant lesions and searched for miR-1 targets.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Leone
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Angelo
authors.forename: Ileana
authors.initials: I
authors.lastname: Rubio
authors.forename: Paula Mussnich
authors.initials: PM
authors.lastname: de Freitas
authors.forename: Antonella
authors.initials: A
authors.lastname: Federico
authors.forename: Marianna
authors.initials: M
authors.lastname: Colamaio
authors.forename: Pierlorenzo
authors.initials: P
authors.lastname: Pallante
authors.forename: Geraldo
authors.initials: G
authors.lastname: Medeiros-Neto
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: C080336:CCND2 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D056742:Cyclin D2; C544547:MIRN1 microRNA, human; D035683:MicroRNAs; D019718:Receptors, CXCR4