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

Ailing Zhong1, Hui Zheng1, Hongqin Zhang1

  • 1Department of Clinical Laboratory, Fudan University, Shanghai Cancer Center, Shanghai, China.

Journal of Cancer
|July 2, 2019
PubMed

Insights

Inhibiting the DNA repair enzyme MUS81 activates cell-cycle pathways and sensitizes ovarian cancer cells to treatments like X-ray and Olaparib, suggesting MUS81 as a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • MUS81 is a crucial endonuclease in DNA double-strand break repair via homologous recombination (HR).
  • Structure-specific endonucleases (SSEs) are vital for DNA replication, repair, and transcription, requiring precise control for genome stability.
  • Previous studies indicated a correlation between MUS81 and CyclinB expression.

Purpose of the Study:

  • To investigate the role of MUS81 in ovarian cancer.
  • To determine if inhibiting MUS81 affects DNA damage repair pathways and chemosensitivity.
  • To evaluate MUS81 as a potential therapeutic target for epithelial ovarian cancer (EOC).

Main Methods:

  • Generated MUS81-downregulated ovarian cancer cells using lentivirus-mediated RNA interference (RNAi).
  • Analyzed the activation of CHK1 and CyclinB signaling pathways.
  • Assessed the sensitivity of these cells to X-ray and Olaparib treatment in vitro and in vivo.

Main Results:

  • Downregulation of MUS81 activated the CHK1 and CyclinB signaling pathways.
  • MUS81 inhibition sensitized ovarian cancer cells to both X-ray and Olaparib treatments.
  • These effects were observed in both in vitro and in vivo models.

Conclusions:

  • MUS81 inhibition represents a promising strategy to enhance the efficacy of existing cancer therapies.
  • Targeting MUS81 could be a viable therapeutic approach for epithelial ovarian cancer (EOC).
  • Further research into MUS81's role in DNA repair and cancer progression is warranted.

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