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

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    Deng_AACR_2014.pdf (2.243Mb)
    Issue Date
    2014-11-15
    Author
    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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    Abstract
    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.
    URI
    http://hdl.handle.net/1808/24052
    DOI
    https://doi.org/10.1158/0008-5472.CAN-13-3710
    Collections
    • Molecular Biosciences Scholarly Works [598]
    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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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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