MUS81 participates in the Progression of Serous Ovarian Cancer Associated with Dysfunctional DNA Repair System

Objective: Methyl methanesulfonateultraviolet sensitive gene clone 81 ( MUS81) is a structure-specific endonuclease that plays an important role in DNA repairsystem of cancer cells. In this study, we aim to investigate potential association between the dysfunction of MUS81and the progression of Serous Ovarian Cancer (SOC). Methods: To investgate the association between MUS81and prognosis of SOC, immunohistochemistry and qPCR were used to analyse the level of MUS81expression, and transcriptional profile analysis and protein interaction screening chip was used to explore the MUS81related signal pathways. Random amplified polymorphic DNA (RAPD) analysis, immunofluorescence and comet assayswere performed to evaluate genomic instabilityand DNA damage status of transduced SOC cells. Experiments both in vitro and in vivo were conducted to verify the impact of MUS81silencing on chemotherapeutic drug sensitivity to SOC. Results: The overexpression of MUS81in SOC tissues was related to poor clinical outcomes. The data of transcriptional chip showed that MUS81was involved in multiple pathways associated with DNA repair. Deficiency of MUS81intensified the genome instabilityof SOC cells, and promoted the emergence of DSBs and restrained the formation of RAD51foci in SOC cells with exposure to UV. Furthermore, downregulation of MUS81enhanced the sensitivity to Camptothecinand Olaparibin SOC cell lines and xenograft model. Conclusions: MUS81is involved in the progression of SOC and plays an important role of the susceptibility to chemotherapeutic agents. MUS81might represent a novel molecular target for SOC chemotherapy.