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

Research output: Contribution to journalArticlepeer-review

7 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 languageEnglish
Article number2843
JournalInternational Journal of Molecular Sciences
Volume20
Issue number11
DOIs
StatePublished - 1 Jun 2019

Keywords

  • BRCA1
  • DNA repair
  • Ionizing radiation
  • Karyopherin-α2
  • Radioresistance

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