The miR-200 family of microRNAs act to enforce an epithelial phenotype and thereby, suppress the migratory and invasive capacity of cells. Using High-Throughput Sequencing, Cross-Linked Immunoprecipitation (HITS-CLIP), our lab has identified hundreds of genes directly regulated by these microRNAs and note an enrichment of targets associated with signalling pathways upstream of the ERK, AKT and JNK family kinases. We note miR-200 effects ERK and AKT activation in response to EGF. We also find a marked increase in UV-stimulated JNK activation, with different JNK isoforms preferentially activated by miR-200a and miR-200b. We are investigating the contribution of prominent miR-200 target genes (DCBLD2, UBASH3B, CBL, PLCG1, ERRFI1, MAP3K9 etc) we have found in these processes. Interestingly, we also find differential regulation of the EGF receptor (EGFR) by these microRNAs, with miR-200b suppressing EGFR expression through direct microRNA targeting, whilst miR-200a has an opposing effect to increase stability (and/or recycling) of the EGFR protein in conditions of prolonged signalling. Such differential regulation is consistent with a model whereby the miR-200 family decreases cell responsiveness to transient EGF signalling (via miR-200b), but then helps potentiate signalling in conditions of prolonged exposure (via miR-200a).