title: ID1 affects the efficacy of radiotherapy in glioblastoma through inhibition of DNA repair pathways.
abstract: Glioblastoma multiforme (GBM) is characterized by poor therapeutic response and poor overall survival. It is crucial that more effective therapies be developed for the treatment of GBM. Inhibitor of DNA binding protein-1 (ID1) has been shown to maintain the self-renewal capacity of neural stem cells and might be involved in the therapeutic resistance of GBM. In the present study, we explored survival data from the The Cancer Genome Atalas database that were based on ID1 expression for patients diagnosed with primary GBMs. Interestingly, patients with high ID1 expression had better survival than patients with low ID1 expression, and a strong correlation was found between radiotherapy efficacy, ID1 expression, and overall survival. We further investigated the relationship between ID1 expression and the radiosensitivity of glioblastoma using glioblastoma cell lines. The clonogenic formation assay showed that U87 ID1-shRNA cells were much less sensitive to radiation. Moreover, both the results of the γH2AX foci staining assay and the comet assay further revealed that ID1 negatively regulates DNA repair processes by downregulating the expression of genes such as DNA ligase IV (LIG4) and ataxia-telangiectasia-mutated. Additionally, ID1 induces G2/M arrest in U87 cells. Taken together, these results suggest that ID1 may be a new prognostic marker for GBM and have important implications for the therapeutic strategies used to treat GBM patients.
authors: Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors: Qinhua
authors: Q
authors: Guo
authors: Pin
authors: P
authors: Guo
authors: Qing
authors: Q
authors: Mao
authors: Jin
authors: J
authors: Lan
authors: Yingying
authors: Y
authors: Lin
authors: Jiyao
authors: J
authors: Jiang
authors: Yongming
authors: Y
authors: Qiu
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy; D020552:Comet Assay; D004260:DNA Repair / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D016016:Proportional Hazards Models; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1
references: Cell Death Dis. 2011 Dec 08;2:e241
references: 22158480
references: Cancer Cell. 2012 Jan 17;21(1):11-24
references: 22264785
references: Acta Neuropathol. 2007 Aug;114(2):97-109
references: 17618441
references: J Biol Chem. 2007 Nov 16;282(46):33284-33294
references: 17855368
references: Cancer Cell. 2010 Dec 14;18(6):655-68
references: 21156287
references: Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1260-5
references: 17227850
references: Neurol Res Int. 2012;2012:878425
references: 22530127
references: Oral Oncol. 2010 Mar;46(3):154-7
references: 20056476
references: N Engl J Med. 2005 Mar 10;352(10):987-96
references: 15758009
references: Nat Rev Cancer. 2008 Mar;8(3):180-92
references: 18273037
references: Nat Rev Cancer. 2005 Aug;5(8):603-14
references: 16034366
references: Stem Cells. 2012 Jul;30(7):1362-72
references: 22511267
references: Biochem Biophys Res Commun. 2011 Aug 26;412(2):253-9
references: 21820417
references: N Engl J Med. 2005 Mar 10;352(10):997-1003
references: 15758010
references: Br J Radiol. 2008 Oct;81 Spec No 1:S6-11
references: 18820000
references: Int J Hematol. 2012 Mar;95(3):239-45
references: 22351161
references: Nucleic Acids Res. 2012 Sep 1;40(17):8348-60
references: 22735704
references: Clin Cancer Res. 2010 Jan 1;16(1):99-108
references: 20008842
references: PLoS One. 2007 Dec 19;2(12):e1338
references: 18092003
references: Biochem Biophys Res Commun. 2011 Aug 19;412(1):39-43
references: 21787748
references: Expert Opin Investig Drugs. 2012 Sep;21(9):1247-66
references: 22731981
references: Mol Cell Biol. 1997 Oct;17(10):5888-96
references: 9315646
references: Oncogene. 1999 Aug 26;18(34):4767-76
references: 10490810
references: Cancer Cell. 2012 Jun 12;21(6):777-92
references: 22698403
references: Cancer Biol Ther. 2010 Aug 1;10(3):299-307
references: 20574154
references: Cancer Cell. 2003 Jun;3(6):525-30
references: 12842081
references: Cancer Treat Rev. 2009 Nov;35(7):590-6
references: 19635647
references: Phytother Res. 2011 Jul;25(7):1095-7
references: 22692988
references: Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):928-42
references: 15234026
references: Mol Cell Biol. 2011 Jul;31(14):3052-67
references: 21606196
references: Cancer Res. 2010 Apr 15;70(8):3239-48
references: 20388787