Cui Yuxin, Wu B O, Flamini Valentina, Evans Bronwen A J, Zhou Deshan, Jiang Wen G
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K.
Department of Histology and Embryolog, Cancer Institute, Key Laboratory of Cancer Metastasis (Beijing), Capital Medical University, Beijing, P.R. China.
Anticancer Res. 2017 Aug;37(8):4415-4424. doi: 10.21873/anticanres.11836.
BACKGROUND/AIM: Overexpression of erythropoietin-producing hepatocellular A1 (EPHA1), a member of the EPH super family, is frequently observed in various cancer types. The dysregulated interaction of EPHA1 with its ligand Ephrin A1 has been linked to the progression of ovarian cancer (OC). However, the contribution of EPHA1 in the regulation of the aggressive properties of OC cells remains unknown.
In this study we investigated the differential expression of EPHA1 in human OC cells. The EPHA1 gene was knocked-down using the CRISPR/Cas9 technique to evaluate its effect on the progressive properties of OC cells.
After EPHA1 was knocked-down using a CRISPR/CAS9 genomic editing system in OC cells (SKOV3 and COV504), we observed cell-cycle arrest at the G/G phases in both OC cell lines. Knockdown of EPHA1 in the two OC cells inhibited their aggressive traits, including proliferation, invasion and migration, as well as improving their attachment to extracellular matrix. EPHA1 may play a role in OC through its regulation of multiple signaling pathways, such as matrix metalloproteinase-2 (MMP2), extracellular signal-regulated kinase 2 (ERK2) and proto-oncogene c-MYC.
EPHA1 may promote the aggression of some OC cells and, thus, be considered a potential therapeutic target for the treatment of malignant OC.
背景/目的：促红细胞生成素产生肝细胞A1（EPHA1）是EPH超家族的成员，在多种癌症类型中经常观察到其过表达。EPHA1与其配体Ephrin A1之间失调的相互作用与卵巢癌（OC）的进展有关。然而，EPHA1在调节OC细胞侵袭性特性中的作用仍不清楚。
在本研究中，我们调查了EPHA1在人OC细胞中的差异表达。使用CRISPR/Cas9技术敲低EPHA1基因，以评估其对OC细胞进展特性的影响。
在OC细胞（SKOV3和COV504）中使用CRISPR/CAS9基因组编辑系统敲低EPHA1后，我们在两种OC细胞系中均观察到细胞周期在G/G期停滞。在两种OC细胞中敲低EPHA1抑制了它们的侵袭性特征，包括增殖、侵袭和迁移，同时改善了它们与细胞外基质的附着。EPHA1可能通过调节多种信号通路，如基质金属蛋白酶-2（MMP2）、细胞外信号调节激酶2（ERK2）和原癌基因c-MYC，在OC中发挥作用。
EPHA1可能促进某些OC细胞的侵袭，因此可被视为治疗恶性OC的潜在治疗靶点。
