RETRACTED ARTICLE: miR-200 Regulates Epithelial–Mesenchymal Transition in Anaplastic Thyroid Cancer via EGF/EGFR Signaling

Abstract

This study was set to study the molecular mechanism underlying how miR-200 regulates EGF/EGFR signaling to involve in epithelial-mesenchymal transition (EMT) in anaplastic thyroid cancer (ATC) cells. Loss-of-function experiments of EGFR silencing by siRNA transfection was performed. Transfection of pre-miR-200s or anti-miR-200s was used to increase or decrease miR-200 transcripts. Real-time PCR, Western blot, immunohistochemistry, and transwell experiments were performed to determine the role of miR-200s in EMT and its role in EGF/EGFR-mediated EMT in vitro and in vivo. EGF/EGFR signaling activation increased the expression of mesenchymal marker vimentin in Nthy-ori 3-1 cells and decreased the expression of endothelial maker E-cadherin. EGF stimulation led to increased RhoA expression in Nthy-ori 3-1 cells. EGFR silencing resulted in decreased RhoA expression in SW1736 and ARO cells. EGF stimulation led to down-regulation of miR-200s and EMT. Restoration of miR-200 expression by pre-miR-200a/c transfection reversed the process, including increased E-cadherin and decreased vimentin. Down-regulation of miR-200 by anti-miR-200 effectively reduced miR-200. Matrigel invasion assay proved that restoration of miR-200 expression counteracted invasiveness. EGFR silencing decreased invasiveness in SW1736 cells, while down-regulation of miR-200s restored invasiveness. Xenograft tumors of SW1736 cells with cotransfection of anti-miR-200s and EGFR siRNA which kept the similar E-cadherin and vimentin expression with the untransfected controls. In ATC cells, miR-200s play a central role in EGF/EGFR-mediated invasiveness in vitro and EMT in vivo.

miR-146a and miR-146b promote proliferation, migration and invasion of follicular thyroid carcinoma via inhibition of ST8SIA4

“…miRNAs are potent gene regulators that have been implicated in multiple pathophysiological processes and may play a crucial role in the progression of thyroid cancer [17, 30–32]. Thus, we sought to determine whether ST8SIA4 expression is controlled by miRNAs.…”

“…Several reports have indicated that miRNAs are associated with thyroid cancer. For example, miR-34a promotes cell proliferation and inhibits apoptosis in PTC [16], whereas miR-200 inhibits epithelial-mesenchymal transition in anaplastic thyroid cancer [17]. However, whether miRNAs suppress ST8SIA and thereby affect the tumour characteristics of FTC remains unknown.…”

miR-182 promotes tumor growth and increases chemoresistance of human anaplastic thyroid cancer by targeting tripartite motif 8

“…A growing number of studies have found that miRNAs function as either onco-miRNAs or tumor suppressors in different steps of human cancers and are associated with tumor initiation, development, and progression 4–6. Some miRNAs are dysregulated in ATC, including miR-618,7 miR-200,8 miR-99a,9 miR-206,10 and miR-20a 11. A recent study reported overexpression of miR-182 in papillary thyroid carcinoma compared to the levels in adjacent normal tissues 12.…”

Multi-omics Signatures and Translational Potential to Improve Thyroid Cancer Patient Outcome

“…Analysis of the expression profile of miR-200s in thyroid cancer showed that ATC and PDTC harbor the lowest expression of miR-200a, miR-200b, and miR-200c as compared with WDTC and normal thyroid tissue [164]. Analysis of the molecular mechanisms modulating miR-200 expression in metastatic thyroid tumors demonstrated the role of EGF/EGFR signaling in the repression of miR-200s through the activation of Rho/ROCK and the TGB-β pathway, and thereby enhancing EMT transcription factor expression and promoting tumor invasiveness [165][166][167]. In agreement with these findings, inhibition of TGFBR1 increased miR-200 expression [164].…”