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
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: | https://repository.cshl.edu/id/eprint/30815 |
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