Page 86 - D. Cancer biology

[D. Cancer biology-57]

Inhibition of Chk1 by miR-320c increases oxaliplatin

susceptibility in triple negative breast cancer

Soo-Been Lee¹, Yesol Kim¹, Sera Lim¹, Jong Hoon Park¹˙*

¹Department of Biological Science, Sookmyung Women's University, Seoul 04310, Republic of Korea

Checkpoint kinase 1 (Chk1) expression is enhanced in most cancers due 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, 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. Our findings suggested that downregulated miR-320c clarified the increased Chk1 expression
in TNBC. 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.