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Inhibition of Chk1 by miR-320c increases oxaliplatin responsiveness in triple-negative breast cancer

 Sera Lim  ;  Yesol Kim  ;  Soo-Been Lee  ;  Hyeok-Gu Kang  ;  Da-Hyun Kim  ;  Jee Won Park  ;  Daeun Chung  ;  Hyunkyung Kong  ;  Kyung Hyun Yoo  ;  Yonghwan Kim  ;  Wonshik Han  ;  Kyung-Hee Chun  ;  Jong Hoon Park 
 ONCOGENESIS, Vol.9(10) : 91, 2020-10 
Journal Title
Issue Date
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.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hyeok Gu(강혁구) ORCID logo https://orcid.org/0000-0002-3187-6844
Chun, Kyung Hee(전경희) ORCID logo https://orcid.org/0000-0002-9867-7321
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