rs12904 polymorphism in the 3'-untranslated region of ephrin A1 ligand and the risk of sporadic colorectal cancer in the Iranian population

Background: Colorectal cancer (CRC) is rated as the second cause of cancer death. Genetic determinants are considered as driving forces in the development of sporadic CRC. Single-nucleotide polymorphisms (SNPs), due to their abundance in the human genome with collectively huge effect on cellular signaling pathways, are attributed as the main genetic factor in disease susceptibility including cancers. MicroRNAs are contributing to posttranslational gene regulation. They exert their regulatory function by binding to their specific recognition sequences located at 3'-untranslated region (UTR) of mRNAs. In the present study, we have elucidated the role of rs12904, a naturally occurring SNP, in the recognition site of miR200c in the 3'UTR of ephrin A1 ligand gene, in the development of sporadic CRC in the Iranian population. Materials and Methods: A case–control study using 152 CRC patients and 160 noncancerous counterparts was conducted to determine the rs12904 genotypes using polymerase chain reaction–restriction fragment length polymorphism method. Results: The results revealed no significant association between the rs12904 and sporadic CRC (odds ratio = 0.97, 95% confidence interval = 0.70–1.34). The frequency of genotypes and also alleles of the mentioned polymorphism were not significantly different between case and control groups (P = 0.765 and P = 0.847, respectively). Conclusion: The results suggest that this polymorphism probably has not a crucial role in the Iranian CRC risk and is not an important potential risk factor in molecular diagnostics of mentioned disease among the Iranian population.

Expression of EphrinA1, vascular endothelial growth factor and microRNA-210 after hydronephrosis / 中国医师杂志

Objective To investigate the difference and correlations of the EphrinA1,vascular endothelial growth factor (VEGF) expression and microRNA (miRNA)-210 in the kidney tissue of rats in the unilateral ureteral obstruction (UUO) model.And to understand the regulation mechanism of the three factors in the occurrence of renal tissue injury in rats.Methods Using unilateral ureteral ligation to establish a model of hydronephrosis in mice (except for the NC group),and they wrere randomly divided into an acute hydronephrosis group (UUO group) and a false surgical control group (NC group).The UUO group was divided into four groups (UUO 2 d group,UUO 5 d group,UUO 9 d group,and UUO 14 d group),and eight mice in each group.The pathological changes of renal tissue were observed by hematoxylin-eosin (HE) staining.Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of EphrinA1,VEGF and miRNA-210;Western blot was used to detect the protein expression of EphrinA1 and VEGF.Resulsts Hydronephrosis was not shown in the NC group,and hydronephrosis and inflammatory cell infiltration were observed in the UUO group.Compared with NC group,the mRNA expression of EphrinA1,VEGF and miRNA-210 were up-regulated in UUO 2 d group (P ＜0.05).With the extension of the time of hydronephrosis,the expressions of all three factors were down-regulated in 9 d and 14 d groups compared with 2 d and 5 d groups,and reached the lowest point at 14 d (P ＜0.05);Western blot result indicated that the expression of EphrinA1 and VEGF in renal tissue of UUO 2 d and 5 d group was increased compared with NC group (P ＜ 0.05).Conclusions The UUO mouse model verified that miRNR-210 participated in hydronephrosis.The consistency of EphrinA1,VEGF,and miRNA-210 indicated that the three factors played an important role in the occurrence and development of UUO.

Expression of EphrinA1, vascular endothelial growth factor and microRNA-210 after hydronephrosis / 中国医师杂志

Objective@#To investigate the difference and correlations of the EphrinA1, vascular endothelial growth factor (VEGF) expression and microRNA (miRNA)-210 in the kidney tissue of rats in the unilateral ureteral obstruction (UUO) model. And to understand the regulation mechanism of the three factors in the occurrence of renal tissue injury in rats.@*Methods@#Using unilateral ureteral ligation to establish a model of hydronephrosis in mice (except for the NC group), and they wrere randomly divided into an acute hydronephrosis group (UUO group) and a false surgical control group (NC group). The UUO group was divided into four groups (UUO 2 d group, UUO 5 d group, UUO 9 d group, and UUO 14 d group), and eight mice in each group. The pathological changes of renal tissue were observed by hematoxylin-eosin (HE) staining. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of EphrinA1, VEGF and miRNA-210; Western blot was used to detect the protein expression of EphrinA1 and VEGF.@*Resulsts@#Hydronephrosis was not shown in the NC group, and hydronephrosis and inflammatory cell infiltration were observed in the UUO group. Compared with NC group, the mRNA expression of EphrinA1 , VEGF and miRNA-210 were up-regulated in UUO 2 d group (P<0.05). With the extension of the time of hydronephrosis, the expressions of all three factors were down-regulated in 9 d and 14 d groups compared with 2 d and 5 d groups, and reached the lowest point at 14 d (P<0.05); Western blot result indicated that the expression of EphrinA1 and VEGF in renal tissue of UUO 2 d and 5 d group was increased compared with NC group (P<0.05).@*Conclusions@#The UUO mouse model verified that miRNR-210 participated in hydronephrosis. The consistency of EphrinA1, VEGF, and miRNA-210 indicated that the three factors played an important role in the occurrence and development of UUO.

Brain-Region Specific Apoptosis Triggered by Eph/ephrin Signaling

Eph receptors and their ligands, ephrins, are abundantly expressed in neuroepithelial cells of the early embryonic brain. Overstimulation of Eph signaling in vivo increases apoptotic cell death of neuroepithelial cells, whereas null mutation of the Eph gene leads to the development of a larger brain during embryogenesis. Thus, it appears that Eph-ephrin signaling plays a role in regulating apoptotic cell death of neuroepithelial cells, thereby influencing brain size during embryonic development. Interestingly, Eph-ephrin signaling is bi-directional, with forward signaling from ephrin- to Eph-expressing cells and reverse signaling from Eph- to ephrin-expressing cells. However, it is not clear whether this forward or reverse signaling plays a role in regulating the size of the neuroepithelial cell population during early brain development. Also, Eph receptors and their corresponding ligands are mutually exclusive in their expression domains, and they encounter each other only at interfaces between their expression domains. This expression pattern may be a critical mechanism for preventing overstimulation of Eph-ephrin signaling. Nevertheless, Eph receptors are co-expressed with their corresponding ligands in certain brain regions. Recently, two studies demonstrated that brain region-specific apoptosis may be triggered by the overlapping expression of Eph and ephrin, a theme that will be explored in this mini-review.

Ephrin A4 expression in osteosarcoma, impact on prognosis, and patient outcome.

Background : Ephrin A4 is one of the ephrin ligand molecules belonging to the tyrosine kinases receptor family. It was originally identified in a T-lymphoma cell line and seen to be expressed in human adult tissue as well as several tumor types. In our previous study, we showed the unique pattern of ephrin A4 immunohistochemical staining, which differed according to the type of examined bone specimens (normal bone, primary, and metastatic osteosarcoma lesions). The aim of the present study is to evaluate the prognostic impact of ephrin A4 expression in a group of primary osteosarcoma patients. Materials and Methods : Ephrin A4 immunohistochemical expression was carried out on 47 primary osteosarcoma cases. Results : Ephrin A4 was expressed in 82.9% of osteosarcoma cases with cytoplasmic localization in 58.9% of positive cases. The cytoplasmic pattern was significantly associated with aggressive histopathological types of osteosarcoma (P = 0.02), advanced stage (P = 0.04), the presence of metastasis (P = 0.03), inferior response to neoadjuvent chemotherapy (P = 0.04), and tended to be associated with a shorter event-free survival (P = 0.09). Conclusions : The cytoplasmic pattern of ephrin A4 could identify a subgroup of primary osteosarcoma patients with a high liability for progression, poor prognosis, and inferior response to chemotherapy.

Ectopic Expression of Ephrin-A5 Under the EphA8 Promoter at the Anterior Region of the Superior Colliculus

EphA/ephrin-A mediated signaling has emerged as a key mechanism regulating axon guidance and topographic mapping, particularly in the well-characterized visual system from the retina to the superior colliculus (SC). In this study, EphA8 bacterial artificial chromosome (BAC) was manipulated to contain a floxed eGFP and human ephrin-A5 expression cassette using homologous recombination method. In the mice containing the recombinant BAC, it was shown that GFP is expressed in an anterior>posterior gradient in the SC. Furthermore, when these mice were crossed with the transgenic mice expressing Cre under the EphA8 promoter, it was evident that a GFP expression cassette was eliminated, and that human ephrin-A5 was ectopically expressed in the anterior region of the SC. This transgenic model would be useful to analyze the role of ephrin-A5 in the SC during the retinocollicular topography formation.

PI_3 K/Akt signal effects Ephrin-A1 mediated malignancy of HCC cells / 中华普通外科杂志

Objective To investigate the role of PI_3 K/Akt signal pathway in Ephrin-Al gene mediated invasion,metastasis of Huh-7 cells.Methods Western blot was used to test the protein expression of phosphatidylinositol 3-kinase(PI_3 K)and mitogen-activated protein kinase(MAPK)after Huh-7 cells were treated with Ephrin-A1/Fc fusion protein.According to the protein expression,LY294002 was used to block PI_3 K/Akt pathway specifically,then p-Akt protein expression,mobility and invasive ability of Huh-7 cells were examined.Results In Huh-7 cells actived by Ephrin-Al/Fc fusion protein,p-Akt expression was higher than that in control group(t=4.564,P＜0.05),but there was no difference of p-p38MAPK expression between Ephrin-Al/Fc fusion protein group and IgG/Fc fusion protein group(P＞0.05).PI_3 K/Akt pathway was specifically blocked by LY294002,the p-Akt protein expression decreased in Huh-7 cells,and the mobility and invasive ability mediated by Ephrin-Al in Huh-7 cells decreased(P＜0.05).Conclusions PI_3 K/Akt pathway effects an important role in mobility and invasive ability of Huh-7 cells mediated by Ephrin-A1.

The relationship between the expression of Ephrin-A1 and its receptor to angiogenesis in HCC / 中国普通外科杂志

Objective To study the relationship between Ephrin-A1 and its receptor with angiogenesis in hepatocellular carcinoma(HCC).Methods Immunohistochemistry staining method(S P methods)and reverse transcription polymerase chain reaction(RT-PCR) were used to determine the protein and mRNA expression of Ephrin-A1 and its receptor EphA1、EphA2 in tumor tissues and their corresponding adjacent liver tissues from 52 HCC patients;then,analyse of the relationship between Ephrin-A1 and clinicopathologyfactor and microvessel density(MVD) in HCC was made.Results The protein expression rate of Ephrin-A1 and EphA1,EphA2 in HCC was 59.6%(31/52),53.8%(28/52)and 17.3%(9/52),respectively,but in the paired liver tissues adjacent to HCC the expression rate was 23.1%(12/52),and respectively.The protein expression rate of Ephrin-A1 and EphA1 was significantly higher than that in the paired liver tissues adjacent to HCC(P0.05).The mRNA express rate of Ephrin-A1 and EphA1 in HCC [67.3%(35/52) and 73.7%(38/52)] were prominently higher than those in the paired liver tissues adjacent to HCC [42.3%(22/52) and 48.1%(25/52)](P0.05).The higher expression of Ephrin-A1 was correlated with the AFP level and thrombus in the portal vein(P