Page 85 - D. Cancer biology

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

Soo-Been Lee, Yesol Kim, Sera Lim and Jong Hoon Park*
Department of Biological Science, Sookmyung Women’s University, Seoul 04310, Republic of Korea
BACKGROUND AIM
Breast cancer is the most common cancers in women worldwide, and DNA damage activates DNA damage response (DDR) by signaling
triple-negative breast cancer (TNBC) is one of its most aggressive forms. pathways mediated by Rad9-Hus1-Rad1(9-1-1)-ATR-Chk1. In
In general, the survival of cancer cells relies on buffering the addition, it was reported that there are several miRNAs known to
consequences of increased stress levels, such as DNA damage and regulate Chk1 in non-small cell lung cancer. However, there is no
replication stress, induced during the tumorigenic process. MicroRNAs study about the effect of miRNA on the responsiveness to
(miRNAs) are small non-coding RNAs, which regulate gene expression oxaliplatin in TNBC by regulating Chk1. In this study, we
by binding to the 3' -untranslated region (UTR) of target mRNAs and it demonstrate that miR-320c may serve as a prognostic marker of
may play a role in drug responsiveness and resistance by altering target oxaliplatin by regulating DDR through the expression of Chk1.
gene expression in breast cancer.
METHODS
▪ Cell viability assay ▪ Alkaline Comet assay ▪ Immunofluorescence(ICC/IF) microscopy ▪ Analysis of human breast tumor microarray data
▪ Dual-Luciferase reporter assay ▪ Apoptosis analysis (FACS) ▪ Caspase-3 activation assay ▪ Xenograft mice and intratumoral miRNA transfection
RESULTS
A B A C

B D

▲ Figure 1. miR-320c expression is downregulated in TNBC
▲ Figure 2. Chk1 expression is negatively regulated by miR-320c binding
A B A

▲ Figure 3. Upregulated miR-320c inhibits clonogenic survival
by regulating Chk1, in vitro ▲ Figure 5. Increase of miR-320c induce DNA damage accumulation by
regulating Chk1
A B A B C

▲ Figure 6. miR-320c mimic downregulates the drug response, in vivo

▲ Figure 4. Upregulation of miR-320c increase Apoptosis by modulating
Chk1 expression
CONCLUSION REFERENCES ACKNOWLEDGEMENTS

▪ Wahba HA, El-Hadaad HA. Current approaches in This work was supported by; the National Research
treatment of triple-negative breast cancer. Cancer Biol Med Foundation of Korea (NRF) Grant funded by the Korean
2015; 12: 106-116. Government (MSIP) (No. 2019R1A2B5B03069738,
NRF-2016R1A5A1011974, and 2015M3A9B6027555).
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▪ Jong Hoon Park, Ph.D.
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