MiRNA-A* contributes to the commitment of mammary epithelial cells to the EMT program during cancer development'.

Using our model of mammary carcinogenesis based on the rat epithelial cell line LA7 that recapitulates the entire process of tumor development including metastasis formation, we identified miRNA-a* upregulated during EMT occurring in vivo after the xenograft of a single LA7 cell in recipient mice. We show that cytokines known to induce EMT, trigger Twist1 dependent miRNA-a* up-regulation. We demonstrate that ectopic expression of miRNA-a* in LA7 recapitulates the mesenchymal-like phenotype. The down-regulation of miRNA-a* abrogates the invasion capacity of the LA7 in 3D in vitro cultures and the metastasis formation in vivo. Our study reveals a miRNA dependent mechanism for the commitment of mammary epithelial cells to the EMT program during cancer development.