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

被引：37

作者：

de Araujo, Patricia Rosa ^{[1
,2
]}

Gorthi, Aparna ^{[1
,2
]}

da Silva, Acarizia E. ^{[1
,2
]}

Tonapi, Sonal S. ^{[1
,2
]}

Vo, Dat T. ^{[1
,2
,5
]}

Burns, Suzanne C. ^{[1
]}

Qiao, Mei ^{[1
]}

Uren, Philip J. ^{[3
]}

Yuan, Zhi-Min ^{[4
]}

Bishop, Alexander J. R. ^{[1
,2
]}

Penalva, Luiz O. F. ^{[1
,2
]}

机构：

[1] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA

[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA

[3] Univ Southern Calif, Mol & Computat Biol Sect, Div Biol Sci, Los Angeles, CA USA

[4] Harvard Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA USA

[5] Univ Texas Southwestern Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2016年 / 186卷 / 09期

关键词：

MESSENGER-RNA TRANSLATION; MICRORNA REPLACEMENT THERAPY; DOUBLE-STRAND BREAKS; CANCER STEM-CELLS; HOMOLOGOUS RECOMBINATION; GLIOMAS; REPAIR; PROLIFERATION; SENSITIVITY; EXPRESSION;

D O I：

10.1016/j.ajpath.2016.05.020

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

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.

引用

页码：2271 / 2278

页数：8

共 47 条

[1] Genomic Analyses of Musashi1 Downstream Targets Show a Strong Association with Cancer-related Processes [J].