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Human Glioma Growth Is Controlled by MicroRNA-10b

  1. Author:
    Gabriely, G.
    Yi, M.
    Narayan, R. S.
    Niers, J. M.
    Wurdinger, T.
    Imitola, J.
    Ligon, K. L.
    Kesari, S.
    Esau, C.
    Stephens, R. M.
    Tannous, B. A.
    Krichevsky, A. M.

  2. Author Address

    [Krichevsky, Anna M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Dept Neurol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. [Ligon, Keith L.] Childrens Hosp Boston, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. [Ligon, Keith L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yi, Ming; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick Inc, Bethesda, MD 20892 USA. [Niers, Johanna M.; Wurdinger, Thomas; Tannous, Bakhos A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Narayan, Ravi S.; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Kesari, Santosh] Univ Calif San Diego, Dept Neurosci, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA. [Esau, Christine] Regulus Therapeut, San Diego, CA USA.;Krichevsky, AM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Dept Neurol, 4 Blackfan Circle,HIM 616, Boston, MA 02115 USA;akrichevsky@rics.bwh.harvard.edu
    1. Year: 2011
    2. Date: May
  2. Journal: Cancer Research
    1. 71
    2. 10
    3. Pages: 3563-3572
  4. Type of Article: Article
  5. ISSN: 0008-5472
  1. Abstract:

    MicroRNA (miRNA) expression profiling studies revealed a number of miRNAs dysregulated in the malignant brain tumor glioblastoma. Molecular functions of these miRNAs in gliomagenesis are mainly unknown. We show that inhibition of miR-10b, a miRNA not expressed in human brain and strongly upregulated in both low-grade and high-grade gliomas, reduces glioma cell growth by cell-cycle arrest and apoptosis. These cellular responses are mediated by augmented expression of the direct targets of miR-10b, including BCL2L11/Bim, TFAP2C/AP-2 gamma, CDKN1A/p21, and CDKN2A/p16, which normally protect cells from uncontrolled growth. Analysis of The Cancer Genome Atlas expression data set reveals a strong positive correlation between numerous genes sustaining cellular growth and miR-10b levels in human glioblastomas, while proapoptotic genes anticorrelate with the expression of miR-10b. Furthermore, survival of glioblastoma patients expressing high levels of miR-10 family members is significantly reduced in comparison to patients with low miR-10 levels, indicating that miR-10 may contribute to glioma growth in vivo. Finally, inhibition of miR-10b in a mouse model of human glioma results in significant reduction of tumor growth. Altogether, our experiments validate an important role of miR-10b in gliomagenesis, reveal a novel mechanism of miR-10b-mediated regulation, and suggest the possibility of its future use as a therapeutic target in gliomas. Cancer Res; 71(10); 3563-72. (C) 2011 AACR.

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External Sources

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  2. DOI: 10.1158/0008-5472.can-10-3568
  3. View record in Web of Science®
  4. WOS: 000290610900014

Library Notes

  1. Fiscal Year: FY2010-2011
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