AIM:To investigate the association between hepatocel-lular carcinoma (HCC) susceptibility and a 12-bp inser-tion/deletion polymorphism (rs6147150) in the 3'UTR of ErbB4.METHODS:Using a case-control design,the rs61...AIM:To investigate the association between hepatocel-lular carcinoma (HCC) susceptibility and a 12-bp inser-tion/deletion polymorphism (rs6147150) in the 3'UTR of ErbB4.METHODS:Using a case-control design,the rs6147150 genotypes in 270 patients with HCC and 270 healthy controls were determined by direct polymerase chain reaction and polyacrylamide gel electrophoresis.Logistic regression was used to analyze the association between the polymorphism and cancer risk.RESULTS:Computational modeling suggested that rs6147150 was located in the seed region of hsa-let-7c,a potential target sequence in ErbB4 3'UTR.Logistic re-gression analysis showed that,compared with individu-als homozygous for wild-type,heterozygotes [adjusted odds ratio (OR)=1.48,95% confidence interval (CI)= 1.03-2.17,P=0.034] and individuals homozygous for 12-bp del/del (OR=2.50,95% CI=1.37-4.56,P=0.001) were at significantly higher risk of HCC.Car-riers of the "del" allele of rs6147150 had a 1.59-fold increased risk for HCC (95% CI=1.22-2.07,P=0.003).CONCLUSION:rs6147150 may be associated with HCC risk,in part through let-7c-mediated regulation,and may be involved in the pathogenesis of HCC in Chi-nese populations.展开更多
Objective: To study the effect of glucocorticoid on the promoter of the pre-receptor glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene. Methods: The 1. 2 kb length sequence u...Objective: To study the effect of glucocorticoid on the promoter of the pre-receptor glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene. Methods: The 1. 2 kb length sequence upstream to the transcription start site of the 11β-HSD1 gene was amplified with polymerase chain reaction (PCR) and then was cloned into pBLCAT6 plasmid carrying chloramphenicol acetyltransferase ( CAT) reporter gene. The plasmid pBLCAT6 carrying the promoter and reporter gene was used to transfect HeLa cells to study the regulation of 11β-HSD1 gene expression by glucocorticoids in terms of reporter gene expression. Results: PCR showed that there was a complete alignment of the amplified sequence with the sequence 1. 2 kb upstream to the transcription start site of 11β-HSD1 gene. When cloned into pBLCAT6 plasmid carrying the reporter gene, this part of the promoter is functional in terms of regulation of reporter gene expression upon transfection into HeLa cells. The synthetic glucocorticoid-dexamethasone induced the reporter gene expression in the system described above, which was blocked by glucocorticoid receptor antagonist RU486. Conclusion: Glucocorticoids can modulate the expression of 11β-HSD1 through a mechanism involving activation of GR and interaction of the promoter of 11β-HSD1 gene.展开更多
基金Supported by The Applied Basic Research Programs of Science and Technology Commission Foundation of Suzhou,No.sys201047
文摘AIM:To investigate the association between hepatocel-lular carcinoma (HCC) susceptibility and a 12-bp inser-tion/deletion polymorphism (rs6147150) in the 3'UTR of ErbB4.METHODS:Using a case-control design,the rs6147150 genotypes in 270 patients with HCC and 270 healthy controls were determined by direct polymerase chain reaction and polyacrylamide gel electrophoresis.Logistic regression was used to analyze the association between the polymorphism and cancer risk.RESULTS:Computational modeling suggested that rs6147150 was located in the seed region of hsa-let-7c,a potential target sequence in ErbB4 3'UTR.Logistic re-gression analysis showed that,compared with individu-als homozygous for wild-type,heterozygotes [adjusted odds ratio (OR)=1.48,95% confidence interval (CI)= 1.03-2.17,P=0.034] and individuals homozygous for 12-bp del/del (OR=2.50,95% CI=1.37-4.56,P=0.001) were at significantly higher risk of HCC.Car-riers of the "del" allele of rs6147150 had a 1.59-fold increased risk for HCC (95% CI=1.22-2.07,P=0.003).CONCLUSION:rs6147150 may be associated with HCC risk,in part through let-7c-mediated regulation,and may be involved in the pathogenesis of HCC in Chi-nese populations.
基金Supported by the National Natural Science Foundation of China(No.39970285),Shanghai Science and Technology Development Project(No.99JC14036)
文摘Objective: To study the effect of glucocorticoid on the promoter of the pre-receptor glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene. Methods: The 1. 2 kb length sequence upstream to the transcription start site of the 11β-HSD1 gene was amplified with polymerase chain reaction (PCR) and then was cloned into pBLCAT6 plasmid carrying chloramphenicol acetyltransferase ( CAT) reporter gene. The plasmid pBLCAT6 carrying the promoter and reporter gene was used to transfect HeLa cells to study the regulation of 11β-HSD1 gene expression by glucocorticoids in terms of reporter gene expression. Results: PCR showed that there was a complete alignment of the amplified sequence with the sequence 1. 2 kb upstream to the transcription start site of 11β-HSD1 gene. When cloned into pBLCAT6 plasmid carrying the reporter gene, this part of the promoter is functional in terms of regulation of reporter gene expression upon transfection into HeLa cells. The synthetic glucocorticoid-dexamethasone induced the reporter gene expression in the system described above, which was blocked by glucocorticoid receptor antagonist RU486. Conclusion: Glucocorticoids can modulate the expression of 11β-HSD1 through a mechanism involving activation of GR and interaction of the promoter of 11β-HSD1 gene.
