title: Musashi1 Impacts Radio-Resistance in Glioblastoma by Controlling DNA-Protein Kinase Catalytic Subunit.
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.
authors.affiliation: 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.
authors.forename: Patricia Rosa
authors.initials: PR
authors.lastname: de Araujo
authors.affiliation: 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.
authors.forename: Aparna
authors.initials: A
authors.lastname: Gorthi
authors.affiliation: 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.
authors.forename: Acarizia E
authors.initials: AE
authors.lastname: da Silva
authors.affiliation: 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.
authors.forename: Sonal S
authors.initials: SS
authors.lastname: Tonapi
authors.affiliation: 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.
authors.forename: Dat T
authors.initials: DT
authors.lastname: Vo
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Burns
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Mei
authors.initials: M
authors.lastname: Qiao
authors.affiliation: Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, California.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Uren
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Alexander J R
authors.initials: AJ
authors.lastname: Bishop
authors.affiliation: 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.
authors.forename: Luiz O F
authors.initials: LO
authors.lastname: Penalva
mesh_terms: D020134:Catalytic Domain / Q000502:physiology; D045744:Cell Line, Tumor; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology*; D021881:DNA, Catalytic; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011116:Polynucleotide 5'-Hydroxyl-Kinase / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011836:Radiation Tolerance / Q000502:physiology*
chemical_list: D021881:DNA, Catalytic; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D011116:Polynucleotide 5'-Hydroxyl-Kinase