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

Autor: Yesol Kim, Hyeok Gu Kang, Hyun Kyung Kong, Yonghwan Kim, Kyung Hyun Yoo, Jong Hoon Park, Da Hyun Kim, Jee Won Park, Lim Sera, Wonshik Han, Daeun Chung, Kyung-Hee Chun, Soo Been Lee
Rok vydání: 2020
Předmět:
Zdroj: Oncogenesis
Oncogenesis, Vol 9, Iss 10, Pp 1-14 (2020)
ISSN: 2157-9024
Popis: 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.
Databáze: OpenAIRE
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