Comprehensive patterns in microRNA regulation of transcription factors during tumor metastasis

In spite of a large body of information about the upstream regulators of metastasis, a process that often plays a limiting factor in therapeutic outcome of cancer patients, the impact of regulatory microRNA patterns remains obscure. This review describes computational analysis of coordinated regulation of genes by di-directional regulation of microRNA and transcription factors that specifically regulate the process of metastasis. We discovered several unexpected modes of regulatory patterns between microRNAs and transcription factors. For example, we found a double positive feedback loop regulated by the hub transcription factor ZEB1 and miR-200 during epithelial–mesenchymal transition. This review further explains flow of information and how such components coordinate various adaptable controls of microRNAs and thus, contribute to regulation of transcription factors in context of cancer metastasis. Information described here provides a regulatory framework for future experimental analyses and discoveries of new insights into post-transcriptional gene regulation at the microRNA level in cancer metastasis. J. Cell. Biochem. 112: 2210–2217, 2011. © 2011 Wiley-Liss, Inc.