Open Access

Cyclosporin A inhibits prostate cancer growth through suppression of E2F8 transcription factor in a MELK‑dependent manner

  • Authors:
    • Da Young Lee
    • Sanghoon Lee
    • Young Sik Kim
    • Soonbum Park
    • Sang-Mun Bae
    • Eun A Cho
    • Eun-Jung Park
    • Hyun Ho Park
    • Sang-Yeob Kim
    • Insuk So
    • Jung Nyeo Chun
    • Ju-Hong Jeon
  • View Affiliations

  • Published online on: October 25, 2023     https://doi.org/10.3892/or.2023.8655
  • Article Number: 218
  • Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The treatment of advanced prostate cancer remains a formidable challenge due to the limited availability of effective treatment options. Therefore, it is imperative to identify promising druggable targets that provide substantial clinical benefits and to develop effective treatment strategies to overcome therapeutic resistance. Cyclosporin A (CsA) showed an anticancer effect on prostate cancer in cultured cell and xenograft models. E2F8 was identified as a master transcription factor that regulated a clinically significant CsA specific gene signature. The expression of E2F8 increased during prostate cancer progression and high levels of E2F8 expression are associated with a poor prognosis in patients with prostate cancer. MELK was identified as a crucial upstream regulator of E2F8 expression through the transcriptional regulatory network and Bayesian network analyses. Knockdown of E2F8 or MELK inhibited cell growth and colony formation in prostate cancer cells. High expression levels of E2F8 and androgen receptor (AR) are associated with a worse prognosis in patients with prostate cancer compared with low levels of both genes. The inhibition of E2F8 improved the response to AR blockade therapy. These results suggested that CsA has potential as an effective anticancer treatment for prostate cancer, while also revealing the oncogenic role of E2F8 and its association with clinical outcomes in prostate cancer. These results provided valuable insight into the development of therapeutic and diagnostic approaches for prostate cancer.
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December-2023
Volume 50 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Lee DY, Lee S, Kim YS, Park S, Bae S, Cho EA, Park E, Park HH, Kim S, So I, So I, et al: Cyclosporin A inhibits prostate cancer growth through suppression of E2F8 transcription factor in a MELK‑dependent manner. Oncol Rep 50: 218, 2023.
APA
Lee, D.Y., Lee, S., Kim, Y.S., Park, S., Bae, S., Cho, E.A. ... Jeon, J. (2023). Cyclosporin A inhibits prostate cancer growth through suppression of E2F8 transcription factor in a MELK‑dependent manner. Oncology Reports, 50, 218. https://doi.org/10.3892/or.2023.8655
MLA
Lee, D. Y., Lee, S., Kim, Y. S., Park, S., Bae, S., Cho, E. A., Park, E., Park, H. H., Kim, S., So, I., Chun, J. N., Jeon, J."Cyclosporin A inhibits prostate cancer growth through suppression of E2F8 transcription factor in a MELK‑dependent manner". Oncology Reports 50.6 (2023): 218.
Chicago
Lee, D. Y., Lee, S., Kim, Y. S., Park, S., Bae, S., Cho, E. A., Park, E., Park, H. H., Kim, S., So, I., Chun, J. N., Jeon, J."Cyclosporin A inhibits prostate cancer growth through suppression of E2F8 transcription factor in a MELK‑dependent manner". Oncology Reports 50, no. 6 (2023): 218. https://doi.org/10.3892/or.2023.8655