Inhibition of karyopherin-α2 augments radiation-induced cell death by perturbing brca1-mediated dna repair

Kyung Hee Song; Seung Youn Jung; Jeong In Park; Jiyeon Ahn; Jong Kuk Park; Hong Duck Um; In Chul Park; Sang Gu Hwang; Hunjoo Ha; Jie Young Song

doi:10.3390/ijms20112843

Inhibition of karyopherin-α2 augments radiation-induced cell death by perturbing brca1-mediated dna repair

Kyung Hee Song, Seung Youn Jung, Jeong In Park, Jiyeon Ahn, Jong Kuk Park, Hong Duck Um, In Chul Park, Sang Gu Hwang, Hunjoo Ha, Jie Young Song

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English
Article number	2843
Journal	International Journal of Molecular Sciences
Volume	20
Issue number	11
DOIs	https://doi.org/10.3390/ijms20112843
State	Published - 1 Jun 2019

Keywords

BRCA1
DNA repair
Ionizing radiation
Karyopherin-α2
Radioresistance

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title = "Inhibition of karyopherin-α2 augments radiation-induced cell death by perturbing brca1-mediated dna repair",

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.",

keywords = "BRCA1, DNA repair, Ionizing radiation, Karyopherin-α2, Radioresistance",

author = "Song, {Kyung Hee} and Jung, {Seung Youn} and Park, {Jeong In} and Jiyeon Ahn and Park, {Jong Kuk} and Um, {Hong Duck} and Park, {In Chul} and Hwang, {Sang Gu} and Hunjoo Ha and Song, {Jie Young}",

note = "Funding Information: Funding: This work was supported by grants from the National Research Foundation of Korea (NRF-2017M2A2A7A01019214) and the Korea Institute of Radiological and Medical Sciences, funded by Ministry of Science and ICT, Republic of Korea (50531-2018). Funding Information: This work was supported by grants from the National Research Foundation of Korea (NRF-2017M2A2A7A01019214) and the Korea Institute of Radiological and Medical Sciences, funded by Ministry of Science and ICT, Republic of Korea (50531-2018). Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/ijms20112843",

language = "English",

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AU - Song, Kyung Hee

AU - Jung, Seung Youn

AU - Park, Jeong In

AU - Ahn, Jiyeon

AU - Park, Jong Kuk

AU - Um, Hong Duck

AU - Park, In Chul

AU - Hwang, Sang Gu

AU - Ha, Hunjoo

AU - Song, Jie Young

N1 - Funding Information: Funding: This work was supported by grants from the National Research Foundation of Korea (NRF-2017M2A2A7A01019214) and the Korea Institute of Radiological and Medical Sciences, funded by Ministry of Science and ICT, Republic of Korea (50531-2018). Funding Information: This work was supported by grants from the National Research Foundation of Korea (NRF-2017M2A2A7A01019214) and the Korea Institute of Radiological and Medical Sciences, funded by Ministry of Science and ICT, Republic of Korea (50531-2018). Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

KW - BRCA1

KW - DNA repair

KW - Ionizing radiation

KW - Karyopherin-α2

KW - Radioresistance

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Inhibition of karyopherin-α2 augments radiation-induced cell death by perturbing brca1-mediated dna repair

Abstract

Keywords

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