Role of microRNA221 in regulating normal mammary epithelial hierarchy and breast cancer stem-like cells

Archive ouverte

Ke, Jia | Zhao, Zhiju | Hong, Su-Hyung | Bai, Shoumin | He, Zhen | Malik, Fayaz | Xu, Jiahui | Zhou, Lei | Chen, Weilong | Martin-Trevino, Rachel | Wu, Xiaojian | Lan, Ping | Yi, Yongju | Ginestier, Christophe | Ibarra, Ingrid | Shang, Li | Mcdermott, Sean | Luther, Tahra | Clouthier, Shawn G. | Wicha, Max S. | Liu, Suling

Edité par CCSD ; Impact journals -

International audience. 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 knockdown 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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion