microRNA100 inhibits self-renewal of breast cancer stem-like cells and breast tumor development

Deng, L., Shang, L., Bai, S., Chen, J., He, X., Trevino, R. M., Chen, S., Li, X., Meng, X., Yu, B., Wang, X., Liu, Y., McDermott, S. P., Ariazi, A. E., Ginestier, C., Ibarra, I., Ke, J., Luther, T. K., Clouthier, S. G., Xu, L., Shan, G., Song, E., Yao, H., Hannon, G. J., Weiss, S. J., Wicha, M. S., Liu, S. (September 2014) microRNA100 inhibits self-renewal of breast cancer stem-like cells and breast tumor development. Cancer Res, 74 (22). pp. 6648-6660. ISSN 0008-5472

URL: http://www.ncbi.nlm.nih.gov/pubmed/25217527
DOI: 10.1158/0008-5472.can-13-3710

Abstract

microRNAs are essential for self-renewal and differentiation of normal and malignant stem cells by regulating the expression of key stem cell regulatory genes. Here we report evidence implicating the microRNA100 (miR-100) in self-renewal of cancer stem-like cells (CSC). We found that miR-100 expression levels relate to the cellular differentiation state with lowest expression in cells displaying stem cell markers. Utilizing a tetracycline-inducible lentivirus to elevate expression of miR-100 in human cells, we found that increasing mir-100 levels decreased the production of breast CSCs. This effect was correlated with an inhibition of cancer cell proliferation in vitro and in mouse tumor xenografts due to attenuated expression of the CSC regulatory genes SMARCA5, SMARCD1 and BMPR2. Furthermore, miR-100 induction in breast CSC immediately upon their orthotopic implantation or intracardiac injection completely blocked tumor growth and metastasis formation. Clinically, we observed a significant association between miR-100 expression in breast cancer specimens and patient survival. Our results suggest that miR-100 is required to direct CSC self-renewal and differentiation.

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
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL labs > Hannon lab
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: Matt Covey
Date: 12 September 2014
Date Deposited: 24 Sep 2014 15:43
Last Modified: 04 Nov 2015 16:06
PMCID: PMC4370193
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30815

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving