Epithelial-Mesenchymal Transition (EMT) describes a reversible process through which changes in gene expression result in a phenotypic switch which affects the migratory and invasive potential of cells. The miR-200 family of microRNAs are essential players in this process, enforcing an epithelial phenotype and decreasing cell migration. Along with miR-200 however, the over-expression of dozens of microRNAs have similarly been associated with EMT, though in many of these studies the degree of enforced expression far exceeds any endogenous levels. Using a human mammary cell line (HMLE cells) as a model of EMT and a combination of wet-bench experimentation and bioinformatic analysis, we find it is the combination of multiple co-regulated microRNAs that regulate EMT, synergistically combining to target common genes or different genes within common pathways to elicit effects. We find that microRNAs also provide an additional regulatory layer that works closely with transcription factors, providing a post-transcriptional mechanism that both buffers transcriptional noise and reinforces transcriptional regulation to drive gene expression during EMT/MET.

References:

Bracken CP, Scott HS, Goodall GJ. “A network-biology perspective of microRNA function and dysfunction in cancer”. Nature Reviews Genetics, 2016 (in press)

Bracken CP, Khew-Goodall Y, Goodall GJ. “Network-Based Approaches to Understand the Roles of miR-200 and Other microRNAs in Cancer”. Cancer Research, 75(13):2594-99, 2015.

Cursons J, Leuchowius KJ, Waltham M, Tomaskovic-Crook E, Foroutan M, Bracken CP, Redfern A, Crampin EJ, Street I, Davis MJ, Thompson EW. “Stimulus-dependent differences in signalling regulate epithelial-mesenchymal plasticity and change the effects of drugs in breast cancer cell lines”. Cell Communication and Signalling. 13:26, 2015 doi: 10.1186/s12964-015-0106-x.