Model of miR-200c regulated chemoresistance.

<p>Treatment of epithelial cells expressing miR-200c with doxorubicin leads to clonal evolution of miR-200c low expressing and mesenchymal-like cells. In consequence, a variety of miR-200c target genes are up-regulated. Besides the induction of EMT by the up-regulation of the E-Cadherin (CDH1) repressors Zeb1 and Zeb2 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050469#pone.0050469-Tryndyak1" target="_blank">[41]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050469#pone.0050469-Li1" target="_blank">[49]</a>, this loss of miR-200c can cause an elevation of resistance factors like TrkB and Bmi1 resulting in enhanced cell survival. This leads to the activation of anti-apoptotic pathways like the phosphorylation of Akt or the degradation of p53, which can be further modulated by a complex crosstalk.