4.7 Article

PCNA-associated factor P15(PAF), targeted by FOXM1, predicts poor prognosis in high-grade serous ovarian cancer patients

Journal

INTERNATIONAL JOURNAL OF CANCER
Volume 143, Issue 11, Pages 2973-2984

Publisher

WILEY
DOI: 10.1002/ijc.31800

Keywords

P15(PAF); FOXM1; HGSOC; PI3K/AKT/mTOR

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Funding

  1. National Natural Science Foundation of China [81572554]
  2. National Science and Technology Project [2015BAI13B05]
  3. Shandong Provincial Natural Science Foundation [ZR2014HM070]
  4. National Key Research and Development Program of China [2016YFC0902903]

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Activation of the FOXM1 signaling pathway and the PI3K/AKT/mTOR signaling pathway is associated with poor prognosis in ovarian cancer. In this study, we demonstrated that P15(PAF) (KIAA0101) was significantly upregulated in high-grade serous ovarian cancer (HGSOC) and that high KIAA0101 expression was associated with poor prognosis. FOXM1 transcriptionally activated KIAA0101 to drive proliferation and metastasis of ovarian cancer cells. KIAA0101 activated the PI3K/AKT/mTOR signaling pathway to inhibit cisplatin-induced apoptosis and autophagy in ovarian cancer cells resulting in cisplatin resistance. Thus, KIAA0101 was closely related to the FOXM1 and PI3K/AKT/mTOR signaling pathways. Collectively, these findings provide insights into the mechanisms of poor prognosis of ovarian cancer and have implications for the development of both predictive and therapeutic biomarkers for the treatment of ovarian cancer.

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