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CDCA8, targeted by MYBL2, promotes malignant progression and olaparib insensitivity in ovarian cancer
Gonghua Qi1, Chenyi Zhang1, Hanlin Ma1,2
1Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University Jinan 250012, China.
Abstract:
Ovarian cancer is the most lethal gynecologic malignancy. Poly (ADP-ribose) polymerase inhibitors (PARPi) are effective in treating ovarian cancer. However, cancer cell insensitivity and resistance remain challenges. Determination of the exact chemoresistance mechanisms and potential targeted therapies is urgent. CDCA8 (cell division cycle associated 8) participates in the tumorigenesis of various cancers; however, the exact biological function of CDCA8 in ovarian cancer remains obscure. Here, we found that CDCA8 was overexpressed in ovarian cancer and that high expression of CDCA8 promoted the proliferation of ovarian cancer cells in vitro and in vivo. Moreover, silencing of CDCA8 sensitized ovarian cancer cells to olaparib and cisplatin by inducing G2/M arrest, accelerating apoptosis, increasing DNA damage and interfering with RAD51 accumulation in vitro. In addition, MYBL2 (MYB proto-oncogene-like 2), identified as an upstream transcription factor of CDCA8, was positively correlated with the expression level of CDCA8 in ovarian cancer. Finally, MYBL2 enhanced the aggressive characteristics of ovarian cancer cells by regulating CDCA8. In conclusion, high CDCA8 expression was involved in the tumorigenesis, aggressiveness and chemoresistance of ovarian cancer. CDCA8 silencing combined with olaparib treatment might lead to substantial progress in ovarian cancer targeted therapy.
Insights
High expression of cell division cycle associated 8 (CDCA8) promotes ovarian cancer growth and chemoresistance. Silencing CDCA8 sensitizes cancer cells to therapies like olaparib, offering a potential targeted treatment strategy.
Area of Science:
- Gynecologic Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Ovarian cancer is a highly lethal gynecologic malignancy.
- Poly (ADP-ribose) polymerase inhibitors (PARPi) show efficacy, but chemoresistance is a significant challenge.
- The role of cell division cycle associated 8 (CDCA8) in ovarian cancer remains unclear.
Purpose of the Study:
- To investigate the biological function of CDCA8 in ovarian cancer.
- To determine the relationship between CDCA8 expression and chemoresistance.
- To explore potential therapeutic strategies targeting CDCA8.
Main Methods:
- Analysis of CDCA8 expression in ovarian cancer tissues.
- In vitro and in vivo studies on CDCA8's role in cell proliferation.
- Assessment of CDCA8 silencing effects on chemoresistance to olaparib and cisplatin.
- Investigation of MYBL2 as an upstream regulator of CDCA8.
Main Results:
- CDCA8 was overexpressed in ovarian cancer, promoting tumor cell proliferation.
- CDCA8 silencing sensitized ovarian cancer cells to olaparib and cisplatin by inducing G2/M arrest, apoptosis, and DNA damage, while interfering with RAD51.
- MYBL2, an upstream regulator, positively correlated with CDCA8 expression and enhanced cancer cell aggressiveness.
Conclusions:
- High CDCA8 expression contributes to ovarian cancer tumorigenesis, aggressiveness, and chemoresistance.
- CDCA8 silencing is a promising strategy to overcome chemoresistance.
- Combined CDCA8 silencing and olaparib treatment may advance ovarian cancer targeted therapy.
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