PCNA-associated factor P15PAF, targeted by FOXM1, predicts poor prognosis in high-grade serous ovarian cancer patients
PCNA-associated factor P15PAF, targeted by FOXM1, predicts poor prognosis in high-grade serous ovarian cancer patients
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DOI：
10.1002/ijc.31800
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发表时间：
2018-12-01
影响因子：
6.4
通讯作者：
Kong, Beihua
中科院分区：
文献类型：
--
作者：
Jin, Chengjuan;Liu, Zhaojian;Kong, Beihua
FOXM 1信号通路和PI 3 K/AKT/mTOR信号通路的激活与卵巢癌的不良预后相关。在这项研究中，我们证明了P15（PAF）（KIAA 0101）在高级别浆液性卵巢癌（HGSOC）中显著上调，KIAA 0101高表达与预后不良相关。FOXM 1转录激活KIAA 0101以驱动卵巢癌细胞的增殖和转移。KIAA 0101激活PI 3 K/AKT/mTOR信号通路，抑制顺铂诱导的卵巢癌细胞凋亡和自噬，导致顺铂耐药。因此，KIAA 0101与FOXM 1和PI 3 K/AKT/mTOR信号通路密切相关。总的来说，这些发现为卵巢癌预后不良的机制提供了见解，并对开发用于治疗卵巢癌的预测性和治疗性生物标志物具有意义。
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.