LAUSR

ABSTRACT The miR‐200 family of microRNAs consisting of miR‐141, miR‐200a, miR‐200b, miR‐200c and miR‐429 are emerging as important regulators of breast cancer progression. This family of microRNAs maintain mammary epithelial identity and downregulation of miR‐200 expression has been associated with epithelial‐to‐mesenchymal transition in mammary tumors. Therefore, re‐expression of one or more miR‐200 family members in mammary tumor cells with mesenchymal characteristics may restore an epithelial phenotype including growth and metastasis suppression. To test this hypothesis, the miR‐200b/200a/429 cluster was re‐expressed in a murine claudin‐low cell line, RJ423. Re‐expression of the miR‐200b/200a/429 cluster in RJ423 cells significantly suppressed the expression of Vim, Snai1, Twist1, Twist2 and Zeb1, reverted RJ423 cells to a more epithelial morphology and significantly inhibited proliferation in vitro. Moreover, the miR‐200b/200a/429 cluster prevented lung metastasis in an experimental metastasis model and although tumor initiation was not prevented, re‐expression of the miR‐200b/200a/429 cluster induced a dormancy‐like state where mammary tumors failed to grow beyond ˜150mm3 or grew extremely slowly following intra‐mammary injection. These dormant tumors contained elevated levels of collagen and were highly vascularized. Therefore, re‐expression of the miR‐200b/200a/429 cluster in the claudin‐low mammary tumor cell line, RJ423, is sufficient to alter cell morphology, impair metastasis and induce tumor dormancy. HIGHLIGHTSmiR‐200 family members regulate mesenchymal gene expression and cell shape.Expression of miR‐200b/200a/429 impairs mammary tumor metastasis.miR‐200b/200a/429 reduces tumor incidence and induces tumor dormancy.