miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions

Recently, the inhibition of epithelial-mesenchymal-transition (EMT) by p53 has been described as a new mode of tumor suppression which presumably prevents metastasis. Here we report that activation of p53 down-regulates the EMT-inducing transcription factor SNAIL via induction of the miR-34a/b/c genes. Suppression of miR-34a/b/c caused up-regulation of SNAIL and cells displayed EMT markers and related features, as enhanced migration and invasion. Ectopic miR-34a induced mesenchymal-epithelial-transition (MET) and down-regulation of SNAIL, which was mediated by a conserved miR-34a/b/c seed-matching sequence in the SNAIL 3'-UTR. miR-34a also down-regulated SLUG and ZEB1, as well as the stemness factors BMI1,…