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

Ke, J., Zhao, Z., Hong, S. H., 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, S. G., Wicha, M. S., Liu, S. (January 2015) Role of microRNA221 in regulating normal mammary epithelial hierarchy and breast cancer stem-like cells. Oncotarget, 6 (6). p. 3709. ISSN 1949-2553

URL: http://www.ncbi.nlm.nih.gov/pubmed/25686829

Abstract

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.

Item Type: Paper
Subjects: diseases & disorders > cancer > cancer types > breast cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA

organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Matt Covey
Date: 21 January 2015
Date Deposited: 27 Feb 2015 17:58
Last Modified: 18 Mar 2015 20:46
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31245

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