The miR-200 family regulates the epithelial-mesenchymal transition induced by EGF/EGFR in anaplastic thyroid cancer cells

Zhe Zhang, Ze-Bing Liu, Wei-Min Ren, Xuan-Guang Ye, You-Yuan Zhang
International Journal of Molecular Medicine 2012, 30 (4): 856-62
The miR-200 family was recently identified as a suppressor of epithelial-mesenchymal transition (EMT). The loss or gain of miR-200 family members is associated with cancer invasion. The epidermal growth factor receptor (EGFR) is overexpressed in the majority of anaplastic thyroid cancers (ATCs). The activation of EGFR by its ligand, epidermal growth factor (EGF), activates a signaling cascade that results in the enhanced migration and invasiveness of thyroid cancer cells. However, little is known about the potential interrelationships between EGF/EGFR, miR-200s and the induction of EMT or mesenchymal-epithelial transition (MET) processes. This study aimed to investigate the regulatory role of miR-200s in EMT modulation by EGF/EGFR. Using transfection, real-time reverse transcription PCR and western blot analysis, we found that the EGF treatment of Nthy-ori 3-1 thyroid follicular cells resulted in the downregulation of E-cadherin and the upregulation of vimentin. By contrast, EGFR silencing in SW1736 human thyroid carcinoma cells led to the upregulation of E-cadherin and the downregulation of vimentin. In addition, EGF signaling correlated with the reduced expression of miR-200s and the re-expression of miR-200s abrogated the effects of EGF treatment and restored an epithelial phenotype to EGF-induced Nthy-ori 3-1 cells. Conversely, the silencing of miR-200s in SW1736 cells overcame siEGFR-induced changes in gene expression and phenotype. In addition, we demonstrate that miR-200s play a key role in in vitro EGF/EGFR-mediated thyroid cell invasion and in EMT in vivo. We, therefore, provide a mechanistic link between the miR-200 family and EGF/EGFR, which suggests that miR-200 upregulation may serve as a novel therapeutic strategy for highly invasive thyroid cancers.

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