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


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.

SUBMITTER: Lim S 

PROVIDER: S-EPMC7548284 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Lim Sera S   Kim Yesol Y   Lee Soo-Been SB   Kang Hyeok-Gu HG   Kim Da-Hyun DH   Park Jee Won JW   Chung Daeun D   Kong Hyunkyung H   Yoo Kyung Hyun KH   Kim Yonghwan Y   Han Wonshik W   Chun Kyung-Hee KH   Park Jong Hoon JH  

Oncogenesis 20201011 10


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. A  ...[more]

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