E2f8 induces cell proliferation and invasion through the epithelial–mesenchymal transition and notch signaling pathways in ovarian cancer

Kyung Jin Eoh, Hee Jung Kim, Jong Woo Lee, Lee Kyung Kim, Sun Ae Park, Hyun Soo Kim, Young Tae Kim, Peter J. Koo

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6 Citations (Scopus)

Abstract

Background: Despite the recent research implicating E2F8 (E2F Transcription Factor 8) in cancer, the role of E2F8 in the progression of ovarian cancer has remained unclear. Hence, we explored the bio-functional effects of E2F8 knockdown on ovarian cancer cell lines in vitro and in vivo. Methods: The expression of E2F8 was compared between ovarian cancer and noncancer tissues, and its association with the progression-free survival of ovarian cancer patients was analyzed. To demonstrate the function of E2F8 in cell proliferation, migration, and invasion, we employed RNA interference to suppress E2F8 expression in ovarian cancer cell lines. Finally, the effect of E2F8 knockdown was investigated in a xenograft mouse model of ovarian cancer. Results: Ovarian cancer tissue exhibited significantly higher E2F8 expression compared to that of normal ovarian tissue. Clinical data showed that E2F8 was a significant predictor of progression-free survival. Moreover, the prognosis of the ovarian cancer patients with high E2F8 expression was poorer than that of the patients with low E2F8 expression. In vitro experiments using E2F8-knockdown ovarian cancer cell lines demonstrated that E2F8 knockdown inhibited cell proliferation, migration, and tumor invasion. Additionally, E2F8 was a potent inducer and modulator of the expression of epithelial–mesenchymal transition and Notch signaling pathway-related markers. We confirmed the function of E2F8 in vivo, signifying that E2F8 knockdown was significantly correlated with reduced tumor size and weight. Conclusions: Our findings indicate that E2F8 is highly correlated with ovarian cancer progression. Hence, E2F8 can be utilized as a prognostic marker and therapeutic target against ovarian malignancy.

Original languageEnglish
Article number5813
Pages (from-to)1-16
Number of pages16
JournalInternational journal of molecular sciences
Volume21
Issue number16
DOIs
Publication statusPublished - 2020 Aug 2

Bibliographical note

Funding Information:
Funding: The present study was supported by a faculty research grant of Yonsei University College of Medicine (6-2019-0094), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute under the funding of the Ministry of Health and Welfare, Republic of Korea (HI17C0321), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) under the funding of the Ministry of Education, Science, and Technology (NRF-2018R1D1A1B07049578).

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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