Cyclin F and KIF20A, FOXM1 target genes, increase proliferation and invasion of ovarian cancer cells
Cyclin F and KIF20A, FOXM1 target genes, increase proliferation and invasion of ovarian cancer cells
复制标题
Cyclin F和KIF20A、FOXM1靶基因，增加卵巢癌细胞的增殖和侵袭
DOI：
10.1016/j.yexcr.2020.112212
复制
发表时间：
2020-10-15
影响因子：
3.7
通讯作者：
Kong, Beihua
中科院分区：
文献类型：
--
作者：
Li, Yingwei;Guo, Haiyang;Kong, Beihua
FOXM1在多种人类恶性肿瘤中的表达增加。FOXM1下游参与肿瘤发生发展的靶基因在卵巢癌中尚未完全阐明。在这里，我们发现了卵巢癌中受FOXM1转录调控的SCF(Skp1-Cul1-F-box Protein)复合体底物识别亚单位Cyclin F和Kinesin Family成员KIF20A。因此，Cyclin F和KIF20A在卵巢癌中普遍过表达。在功能上，Cyclin F或KIF20A的强制表达显著增强，而它们的敲除则降低了卵巢癌细胞的增殖和侵袭能力。重要的是，高水平的Cyclin F和KIF20A与卵巢癌患者的不良预后相关。我们的发现表明，Cyclin F和KIF20A是FOXM1的功能靶点，可能是治疗卵巢癌的潜在药物靶点。
Increased expression of FOXM1 is observed in a variety of human malignancies. The downstream target genes of FOXM1 involved in tumorigenesis and development are not fully elucidated in ovarian cancer. Here, we identified Cyclin F, a substrate recognition subunit of SCF (Skp1-Cul1-F-box protein) complex, and Kinesin Family Member 20A (KIF20A) were transcriptionally regulated by FOXM1 in ovarian cancer. Accordingly, Cyclin F and KIF20A were commonly overexpressed in ovarian cancer. Functionally, forced expression of Cyclin F or KIF20A significantly enhanced while knockdown of them decreased proliferation and invasion of ovarian cancer cells. Importantly, high levels of Cyclin F and KIF20A correlated with poor prognosis in patients with ovarian cancer. Our findings indicate that Cyclin F and KIF20A are functional targets of FOXM1 which might be potential drug targets in ovarian cancer.