Downregulation of microRNAs directs the EMT and invasive potential of anaplastic thyroid carcinomas
- 24 May 2010
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 29 (29), 4237-4244
- https://doi.org/10.1038/onc.2010.169
Abstract
Anaplastic thyroid carcinomas (ATCs) arise from epithelial thyroid cells by mesenchymal de-/transdifferentiation and rapidly invade the adjacent tissue. Specific microRNA signatures were suggested to distinguish ATCs from normal thyroid tissue and other thyroid carcinomas of follicular origin. Whether distinct microRNA patterns correlate with de-/transdifferentiation and invasion of ATCs remained elusive. We identified two significantly decreased microRNA families that unambiguously distinguish ATCs from papillary and follicular thyroid carcinomas: miR-200 and miR-30. Expression of these microRNAs in mesenchymal ATC-derived cells reduced their invasive potential and induced mesenchymal-epithelial transition (MET) by regulating the expression of MET marker proteins. Supporting the role of transforming growth factor (TGF)beta signaling in modulating MET/epithelial-mesenchymal transition (EMT), expression of SMAD2 and TGFBR1, upregulated in most primary ATCs, was controlled by members of the miR-30 and/or miR-200 families in ATC-derived cells. Inhibition of TGFbeta receptor 1 (TGFBR1) in these cells induced MET and reduction of prometastatic miR-21, but caused an increase of the miR-200 family. These findings identify altered microRNA signatures as potent markers for ATCs that promote de-/transdifferentiation (EMT) and invasion of these neoplasias. Hence, TGFBR1 inhibition could have a significant potential for the treatment of ATCs and possibly other invasive tumors.Keywords
This publication has 24 references indexed in Scilit:
- Expression of vascular endothelial growth factor is coordinately regulated by the activin-like kinase receptors 1 and 5 in endothelial cellsBlood, 2009
- Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancerNucleic Acids Research, 2009
- The Inhibition of the Highly Expressed Mir-221 and Mir-222 Impairs the Growth of Prostate Carcinoma Xenografts in MicePLOS ONE, 2008
- SMAD proteins control DROSHA-mediated microRNA maturationNature, 2008
- A reciprocal repression between ZEB1 and members of the miR‐200 family promotes EMT and invasion in cancer cellsEMBO Reports, 2008
- MicroRNA Expression Profiling of Thyroid Tumors: Biological Significance and Diagnostic UtilityJournal of Clinical Endocrinology & Metabolism, 2008
- The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2Genes & Development, 2008
- Identification of metastasis-related microRNAs in hepatocellular carcinomaHepatology, 2008
- Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasionProceedings of the National Academy of Sciences of the United States of America, 2007
- ALK5 promotes tumor angiogenesis by upregulating matrix metalloproteinase-9 in tumor cellsOncogene, 2006