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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.
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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.
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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.
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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.
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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