Inhibition of Karyopherin-α2 Augments Radiation-Induced Cell Death by Perturbing BRCA1-Mediated DNA Repair

Autor: Hong Duck Um, Jong Kuk Park, Jeong In Park, Seung Youn Jung, Kyung Hee Song, Jie-Young Song, Jiyeon Ahn, In Chul Park, Hunjoo Ha, Sang-Gu Hwang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Apoptosis
lcsh:Chemistry
0302 clinical medicine
Radiation
Ionizing
RNA
Small Interfering
lcsh:QH301-705.5
Spectroscopy
Gene knockdown
karyopherin-α2
Cell Death
BRCA1 Protein
Chemistry
General Medicine
Computer Science Applications
radioresistance
030220 oncology & carcinogenesis
Comet Assay
ionizing radiation
HT29 Cells
alpha Karyopherins
Programmed cell death
Cell Survival
DNA damage
DNA repair
Blotting
Western
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
Radioresistance
DNA Repair Protein
medicine
Humans
Immunoprecipitation
Physical and Theoretical Chemistry
Molecular Biology
Cell Proliferation
Organic Chemistry
Cancer
HCT116 Cells
medicine.disease
BRCA1
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Cancer research
DNA Damage
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 11, p 2843 (2019)
International Journal of Molecular Sciences
Volume 20
Issue 11
ISSN: 1422-0067
Popis: 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-&alpha
2 (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.
Databáze: OpenAIRE
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