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

Autor:	de Araujo PR; 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., Gorthi A; 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., da Silva AE; 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., Tonapi SS; 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., Vo DT; 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., Burns SC; Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas., Qiao M; Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas., Uren PJ; Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, California., Yuan ZM; Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts., Bishop AJ; 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., Penalva LO; 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.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2016 Sep; Vol. 186 (9), pp. 2271-8. Date of Electronic Publication: 2016 Jul 25.
DOI:	10.1016/j.ajpath.2016.05.020
Abstrakt:	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. (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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