Role of microRNA221 in regulating normal mammary epithelial hierarchy and breast cancer stem-like cells.
Ke J, Zhao Z, Hong SH, Bai S, He Z, Malik F, Xu J, Zhou L, Chen W, Martin-Trevino R, Wu X, Lan P, Yi Y, Ginestier C, Ibarra I, Shang L, McDermott S, Luther T, Clouthier SG, Wicha MS
Increasing evidence suggests that lineage specific subpopulations and stem-like cells exist in normal and malignant breast tissues. Epigenetic mechanisms maintaining this hierarchical homeostasis remain to be investigated. In this study, we found the level of microRNA221 (miR-221) was higher in stem-like and myoepithelial cells than in luminal cells isolated from normal and malignant breast tissue. In normal breast cells, over-expression of miR-221 generated more myoepithelial cells whereas knock-down of miR-221 increased luminal cells. Over-expression of miR-221 stimulated stem-like cells in luminal type of cancer and the miR-221 level was correlated with clinical outcome in breast cancer patients. Epithelial-mesenchymal transition (EMT) was induced by overexpression of miR-221 in normal and breast cancer cells. The EMT related gene ATXN1 was found to be a miR-221 target gene regulating breast cell hierarchy. In conclusion, we propose that miR-221 contributes to lineage homeostasis of normal and malignant breast epithelium.Lire l‘article