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Inhibition of Karyopherin-α2 Augments Radiation-Induced Cell Death by Perturbing BRCA1-Mediated DNA Repair.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2019 Jun 11; Vol. 20 (11). Date of Electronic Publication: 2019 Jun 11. - Publication Year :
- 2019
-
Abstract
- Ionizing radiation (IR) has been widely used in the treatment of cancer. Radiation-induced DNA damage triggers the DNA damage response (DDR), which can confer radioresistance and early local recurrence by activating DNA repair pathways. Since karyopherin-α2 (KPNA2), playing an important role in nucleocytoplasmic transport, was significantly increased by IR in our previous study, we aimed to determine the function of KPNA2 with regard to DDR. Exposure to radiation upregulated KPNA2 expression in human colorectal cancer HT29 and HCT116 cells and breast carcinoma MDA-MB-231 cells together with the increased expression of DNA repair protein BRCA1. The knockdown of KPNA2 effectively increased apoptotic cell death via inhibition of BRCA1 nuclear import following IR. Therefore, we propose that KPNA2 is a potential target for overcoming radioresistance via interruption to DDR.
- Subjects :
- Apoptosis radiation effects
BRCA1 Protein genetics
Blotting, Western
Cell Line, Tumor
Cell Proliferation radiation effects
Cell Survival genetics
Comet Assay
DNA Damage radiation effects
DNA Repair radiation effects
HCT116 Cells
HT29 Cells
Humans
Immunoprecipitation
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Radiation, Ionizing
BRCA1 Protein metabolism
Cell Death radiation effects
Cell Survival physiology
alpha Karyopherins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 20
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31212646
- Full Text :
- https://doi.org/10.3390/ijms20112843