MicroRNA100 Inhibits Self-Renewal of Breast Cancer Stem–like Cells and Breast Tumor Development

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Issue Date
2014-11-15Author
Deng, Lu
Shang, Li
Bai, Shoumin
Chen, Ji
He, Xueyan
Martin-Trevino, Rachel
Chen, Shanshan
Li, Xiao-yan
Meng, Xiaojie
Yu, Bin
Wang, Xiaolin
Liu, Yajing
McDermott, Sean P.
Ariazi, Alexa E.
Ginestier, Christophe
Ibarra, Ingrid
Ke, Jia
Luther, Tahra
Clouthier, Shawn G.
Xu, Liang
Shan, Ge
Song, Erwei
Yao, Heruui
Hannon, Gregory J.
Weiss, Stephen J.
Wicha, Max S.
Liu, Suling
Publisher
American Association for Cancer Research
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
©2014 American Association for Cancer Research.
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Show full item recordAbstract
miRNAs 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 miR100 in self-renewal of cancer stem-like cells (CSC). We found that miR100 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 miR100 in human cells, we found that increasing miR100 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, miR100 induction in breast CSCs immediately upon their orthotopic implantation or intracardiac injection completely blocked tumor growth and metastasis formation. Clinically, we observed a significant association between miR100 expression in breast cancer specimens and patient survival. Our results suggest that miR100 is required to direct CSC self-renewal and differentiation.
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Citation
Deng, L., Shang, L., Bai, S., Chen, J., He, X., Martin-Trevino, R., … Liu, S. (2014). MicroRNA100 Inhibits Self-Renewal of Breast Cancer Stem–like Cells and Breast Tumor Development. Cancer Research, 74(22), 6648–6660. http://doi.org/10.1158/0008-5472.CAN-13-3710
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