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Am J Pathol. 2016 Sep;186(9):2271-8. doi: 10.1016/j.ajpath.2016.05.020. Epub 2016 Jul 25.

Musashi1 Impacts Radio-Resistance in Glioblastoma by Controlling DNA-Protein Kinase Catalytic Subunit.

Author information

1
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas; Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas.
2
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas.
3
Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, California.
4
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts.
5
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas; Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas. Electronic address: bishopa@uthscsa.edu.
6
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas; Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas. Electronic address: penalva@uthscsa.edu.

Abstract

The conserved RNA-binding protein Musashi1 (MSI1) has been characterized as a stem cell marker, controlling the balance between self-renewal and differentiation and as a key oncogenic factor in numerous solid tumors, including glioblastoma. To explore the potential use of MSI1 targeting in therapy, we studied MSI1 in the context of radiation sensitivity. Knockdown of MSI1 led to a decrease in cell survival and an increase in DNA damage compared to control in cells treated with ionizing radiation. We subsequently examined mechanisms of double-strand break repair and found that loss of MSI1 reduces the frequency of nonhomologous end-joining. This phenomenon could be attributed to the decreased expression of DNA-protein kinase catalytic subunit, which we have previously identified as a target of MSI1. Collectively, our results suggest a role for MSI1 in double-strand break repair and that its inhibition may enhance the effect of radiotherapy.

PMID:
27470713
PMCID:
PMC5012509
DOI:
10.1016/j.ajpath.2016.05.020
[Indexed for MEDLINE]
Free PMC Article

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