Katoh Masuko, Katoh Masaru
M&M Medical BioInformatics, Hongo 113-0033, Japan.
Int J Oncol. 2006 May;28(5):1243-7.
EPHA1, EPHA2, EPHA3, EPHA4, EPHA5, EPHA6, EPHA7, EPHA8, EPHA10, EPHB1, EPHB2, EPHB3, EPHB4 and EPHB6 are EPH family receptors for Ephrin family ligands. Ephrin/EPH signaling pathway networks with the WNT signaling pathway during embryogenesis, tissue regeneration, and carcinogenesis. TCF/LEF-binding sites within the promoter region of human EPH family members were searched for by using bioinformatics and human intelligence. Because five TCF/LEF-binding sites were identified within the 5'-promoter region of the EPHA7 gene, comparative genomics analyses on EPHA7 orthologs were further performed. EPHA7-MANEA-FHL5 locus at human chromosome 6q16.1 and EPHA10-MANEAL-FHL3 locus at human chromosome 1p34.3 were paralogous regions within the human genome. Human EPHA7 mRNA was expressed in embryonic stem (ES) cells, neural tissues, duodenal cancer and parathyroid tumors, while mouse Epha7 mRNA was expressed in fertilized egg, Rathke's pouche, visual cortex, pituitary gland, other neural tissues, pancreas, lung tumors and mammary tumors. The chimpanzee EPHA7 gene and cow Epha7 gene were identified within NW_107969.1 and AC155055.2 genome sequences, respectively. Five TCF/LEF-binding sites within human EPHA7 promoter were conserved in the chimpanzee EPHA7 promoter, and three TCF/LEF-binding sites in the cow Epha7 promoter, but none in the mouse Epha7 promoter. Primates and cow EPHA7 orthologs were identified as evolutionarily conserved targets of the WNT/beta-catenin signaling pathway. D6S1056 microsatellite marker within EPHA7 gene is deleted in prostate cancer. Deletion and/or promoter CpG hypermethylation could explain the EPHA7 down-regulation in human tumors. EPHA7 is a target of systems medicine, especially in the fields of regenerative medicine and oncology.
EPHA1、EPHA2、EPHA3、EPHA4、EPHA5、EPHA6、EPHA7、EPHA8、EPHA10、EPHB1、EPHB2、EPHB3、EPHB4和EPHB6是Ephrin家族配体的EPH家族受体。在胚胎发生、组织再生和肿瘤发生过程中，Ephrin/EPH信号通路与WNT信号通路相互作用。利用生物信息学和人工智慧搜索了人类EPH家族成员启动子区域内的TCF/LEF结合位点。由于在EPHA7基因的5'启动子区域内鉴定出五个TCF/LEF结合位点，因此进一步对EPHA7直系同源基因进行了比较基因组学分析。位于人类6号染色体6q16.1的EPHA7-MANEA-FHL5基因座和位于人类1号染色体1p34.3的EPHA10-MANEAL-FHL3基因座是人类基因组中的旁系同源区域。人类EPHA7 mRNA在胚胎干细胞、神经组织、十二指肠癌和甲状旁腺肿瘤中表达，而小鼠Epha7 mRNA在受精卵、拉特克囊、视皮层、垂体、其他神经组织、胰腺、肺肿瘤和乳腺肿瘤中表达。分别在NW_107969.1和AC155055.2基因组序列中鉴定出黑猩猩EPHA7基因和牛Epha7基因。人类EPHA7启动子内的五个TCF/LEF结合位点在黑猩猩EPHA7启动子中保守，在牛Epha7启动子中有三个TCF/LEF结合位点，但在小鼠Epha7启动子中没有。灵长类动物和牛的EPHA7直系同源基因被鉴定为WNT/β-连环蛋白信号通路的进化保守靶点。EPHA7基因内的D6S1056微卫星标记在前列腺癌中缺失。缺失和/或启动子CpG高甲基化可以解释人类肿瘤中EPHA7的下调。EPHA7是系统医学的一个靶点，尤其是在再生医学和肿瘤学领域。
