Inhibition of Karyopherin-2 Augments Radiation-Induced Cell Death by Perturbing BRCA1-Mediated DNA Repair
- 주제(키워드) ionizing radiation , karyopherin-2 , DNA repair , radioresistance , BRCA1
- 주제(기타) Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
- 설명문(일반) [Song, Kyung-Hee; Jung, Seung-Youn; Park, Jeong-In; Ahn, Jiyeon; Park, Jong Kuk; Um, Hong-Duck; Park, In-Chul; Hwang, Sang-Gu; Song, Jie-Young] Korea Inst Radiol & Med Sci, Div Radiat Biomed Res, Seoul 01812, South Korea; [Song, Kyung-Hee; Ha, Hunjoo] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published, Green Submitted
- 발행기관 MDPI
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000159943
- 본문언어 영어
- Published As http://dx.doi.org/10.3390/ijms20112843
- PubMed https://pubmed.ncbi.nlm.nih.gov/31212646
초록/요약
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-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.
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