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MUS81 is associated with cell proliferation and cisplatin sensitivity in serous ovarian cancer
Suhong Xie1, Hui Zheng1, Xuemei Wen2
1Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Abstract:
The dysfunction of DNA damage repair (DDR) pathway contributes to tumorigenesis and drug-resistance in cancer. MUS81 is a member of the conserved xeroderma pigmentosum group F (XPF) family protein of endonucleases, which is important to the DDR pathway. However, the role of MUS81 in the development of ovarian cancer remains uncertain. To explore the expression of MUS81 and its association to serous ovarian cancer (SOC), 43 biopsies of SOC patients were detected by qRT-PCR, and 29 specimens were further performed by immunohistochemistry analysis. Here, we observed that MUS81 was over-expressed in SOC tissues at both transcript and protein levels, and the expression level of MUS81 protein in ovarian cancer cell lines was also higher than that in human normal ovarian surface epithelial cell line (HOSEpiC). We also found that down-regulation of MUS81 expression in ovarian cancer cells inhibited cell proliferation and colony formation ability, and influenced cell cycle progression. Moreover, inhibition of MUS81 expression induced cellular senescence and enhanced the antitumor effect of cisplatin. Down-regulation of MUS81 expression could suppress the growth and development of SOC. These results indicate that MUS81 might play important roles in the progression of SOC and influence the antitumor effect of cisplatin.
Insights
MUS81 is overexpressed in serous ovarian cancer (SOC), promoting tumor growth and cisplatin resistance. Inhibiting MUS81 suppresses SOC progression and enhances chemotherapy effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- DNA damage repair (DDR) pathway dysfunction is linked to cancer development and drug resistance.
- MUS81, an endonuclease in the DDR pathway, has an unclear role in ovarian cancer progression.
Purpose of the Study:
- To investigate the expression of MUS81 in serous ovarian cancer (SOC).
- To determine the association between MUS81 expression and SOC development.
- To evaluate the impact of MUS81 down-regulation on SOC cell behavior and cisplatin sensitivity.
Main Methods:
- Quantitative reverse transcription PCR (qRT-PCR) on 43 SOC patient biopsies.
- Immunohistochemistry analysis on 29 SOC specimens.
- Assessment of MUS81 expression in ovarian cancer cell lines and normal ovarian surface epithelial cells (HOSEpiC).
Main Results:
- MUS81 was significantly overexpressed at both transcript and protein levels in SOC tissues compared to normal controls.
- Ovarian cancer cell lines exhibited higher MUS81 protein levels than HOSEpiC.
- Down-regulation of MUS81 inhibited ovarian cancer cell proliferation, colony formation, and altered cell cycle progression.
- MUS81 inhibition induced cellular senescence and potentiated the antitumor effects of cisplatin.
Conclusions:
- MUS81 overexpression plays a crucial role in the progression of serous ovarian cancer.
- Targeting MUS81 may represent a therapeutic strategy to enhance cisplatin efficacy in SOC treatment.
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