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.

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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