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Human Glioma Growth Is Controlled by MicroRNA-10b
Published version of a preprint
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-2γ, 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. ©2011 AACR.
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“the pro-oncogenic miRNA miR-10b is upregulated in glioblastomas and has recently been shown to be a significant contributor to tumor growth in vivo [9], [17].”
From Reduced Expression of Brain-Enriched microRNAs in Glioblastomas Permits Targeted Regulation of a Cell Death Gene (2011) · cites this paper as [17]
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Cites
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
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p21 in cancer: Intricate networks and multiple activities
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MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators
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Cited by
Sorted by citations
MicroRNA therapeutics: towards a new era for the management of cancer and other diseases
Rupaimoole, R., & Slack, F. J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.246 · Cited by 4,741
Adlakha, Y. K., & Saini, N. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-33 · Cited by 213
Skalsky, R. L., & Cullen, B. R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024248 · Cited by 170
Metadata
- Authors
- 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.
- Affiliations
- Authors' Affiliations: 1Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; 2Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute; 3Department of Pathology, Brigham and Women's Hospital, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts; 4Advanced Biomedical Computing Center, Information Systems Program, SAIC-Frederick Inc, National Cancer Institute, Bethesda, Maryland; 5Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; 6Neuro-Oncology Research Group, Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands; 7Department of Neurosciences, Moores UCSD Cancer Center, University of California at San Diego, La Jolla, California; and 8Regulus Therapeutics, San Diego, California
- Venue
- Cancer Research
- Published
- 2011-05-15
- Volume
- 71
- Issue
- 10
- Pages
- 3563-3572
- ISSN
- 0008-5472
- 1538-7445
- PMC
- PMC3096675
- Cited by
- 266
- References
- 5
- Language
- en
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