J Cancer 2019; 10(10):2276-2287. doi:10.7150/jca.30818 This issue

Research Paper

MUS81 Inhibition Increases the Sensitivity to Therapy Effect in Epithelial Ovarian Cancer via Regulating CyclinB Pathway

Ailing Zhong1,*, Hui Zheng1,*, Hongqin Zhang1, Jiajun Sun1, Jiabin Shen1, Minjie Deng1, Miaomiao Chen1,2, Renquan Lu1,2, Lin Guo1,2✉

1. Department of Clinical Laboratory, Fudan University, Shanghai Cancer Center, Shanghai, China.
2. Department of Oncology, Shanghai, Medical College, Fudan University, Shanghai, China.
* These authors contributed equally.

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Zhong A, Zheng H, Zhang H, Sun J, Shen J, Deng M, Chen M, Lu R, Guo L. MUS81 Inhibition Increases the Sensitivity to Therapy Effect in Epithelial Ovarian Cancer via Regulating CyclinB Pathway. J Cancer 2019; 10(10):2276-2287. doi:10.7150/jca.30818. Available from https://www.jcancer.org/v10p2276.htm

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MUS81 is a key endonuclease involved in homologous recombination (HR) repair after DNA double-strand damage. Structure-specific endonucleases (SSEs) plays a crucial role in DNA replication, repair and transcription, and SSEs are also important for maintaining the secondary structure of DNA; therefore, their activity must be precisely controlled to ensure genome stability. We previously described that MUS81 expression was significantly correlated with CyclinB expression based on protein microarray analysis. CyclinB is a cell-cycle regulatory protein that has been shown to be involved in the activation of DNA damage repair checkpoints by inducing G2/M phase arrest, promoting apoptosis, and participating in the regulation of chemotherapeutic drug sensitivity by inducing nuclear degradation, as shown by immunofluorescence assays. In this study, MUS81-downregulated cells were generated using lentivirus-mediated RNAi. Our results demonstrated that the inhibition of MUS81 expression activated the CHK1 and CyclinB signaling pathways and sensitized ovarian cancer cells to X-ray and Olaparib treatment both in vitro and in vivo. MUS81 may be a potential therapeutic target for epithelial ovarian cancer (EOC).

Keywords: MUS81, CyclinB, Olaparib, DNA damage repair, EOC