Inhibition of Chk1 by miR-320c increases oxaliplatin responsiveness in triple-negative breast cancer
- Authors
- Lim, Sera; Kim, Yesol; Lee, Soo-Been; Kang, Hyeok-Gu; Kim, Da-Hyun; Park, Jee Won; Chung, Daeun; Kong, Hyunkyung; Yoo, Kyung Hyun; Kim, Yonghwan; Han, Wonshik; Chun, Kyung-Hee; Park, Jong Hoon
- Issue Date
- Oct-2020
- Publisher
- SPRINGERNATURE
- Citation
- ONCOGENESIS, v.9, no.10, pp 1 - 14
- Pages
- 14
- Journal Title
- ONCOGENESIS
- Volume
- 9
- Number
- 10
- Start Page
- 1
- End Page
- 14
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/1087
- DOI
- 10.1038/s41389-020-00275-x
- ISSN
- 2157-9024
- Abstract
- Checkpoint kinase 1 (Chk1) expression is enhanced in most cancers owing to oncogenic activation and constant replicative stress. Chk1 inactivation is a promising cancer therapy, as its inactivation leads to genomic instability, chromosomal catastrophe, and cancer cell death. Herein, we observed that miR-320c, downregulated in triple-negative breast cancer (TNBC) patients, can target Chk1. In addition, downregulated miR-320c expression was associated with poor overall survival in TNBC patients. As Chk1 was associated with the DNA damage response (DDR), we investigated the effect of miR-320c on DDR in TNBC cells. To induce DNA damage, we used platinum-based drugs, especially oxaliplatin, which is most effective with miR-320c. We observed that overexpression of miR-320c in TNBC regulated the oxaliplatin responsiveness by mediating DNA damage repair through the negative regulation of Chk1 in vitro. Furthermore, using a xenograft model, a combination of miR-320c mimic and oxaliplatin effectively inhibited tumor progression. These investigations indicate the potential of miR-320c as a marker of oxaliplatin responsiveness and a therapeutic target to increase the efficacy of chemotherapy in TNBC.
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