MicroRNA Regulation of Epithelial to Mesenchymal Transition

Abstract

Epithelial to mesenchymal transition (EMT) is a central regulatory program that is similar in many aspects to several steps of embryonic morphogenesis. In addition to its physiological role in tissue repair and wound healing, EMT contributes to chemo resistance, metastatic dissemination and fibrosis, amongst others. Classically, the morphological change from epithelial to mesenchymal phenotype is characterized by the appearance or loss of a group of proteins which have come to be recognized as markers of the EMT process. As with all proteins, these molecules are controlled at the transcriptional and translational level by transcription factors and microRNAs, respectively. A group of developmental transcription factors form the backbone of the EMT cascade and a large body of evidence shows that microRNAs are heavily involved in the successful coordination of mesenchymal transformation and vice versa, either by suppressing the expression of different groups of transcription factors, or otherwise acting as their functional mediators in orchestrating EMT. This article dissects the contribution of microRNAs to EMT and analyzes the molecular basis for their roles in this cellular process. Here, we emphasize their interaction with core transcription factors like the zinc finger enhancer (E)-box binding homeobox (ZEB), Snail and Twist families as well as some pluripotency transcription factors.

Keywords: EMT; MET; cancer; microRNAs; transcription factor.

Figure 1

Schematic representation of EMT de-regulating transcription factors and the major key players in the regulation of EMT (down regulation is shown by red downward arrows and up regulation by red upward arrows).

Figure 2

Overview of significant miRNAs involved in EMT regulation. This is specific to transcription factors only and includes microRNAs targeting transcription factors and microRNAs enhanced or repressed by transcription factor activity. An up-regulation/activation is shown by green arrows and translational/transcriptional repression, or -inhibition by red truncated lines.