A nucleotide variant in promoter of the human CDH13 gene which affects its transcription activity is associated with colorectal cancer

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• 作者：Injung Kim (1)
  Jongkeun Park (1)
  Jeong-Ki Kim (1)
  Bong-Kyu Kim (1)
  Hwayoung Lee (1)
  Keonwoo Choi (1)
  Jong-Bok Yoon (2)
  Sungjoo Kim Yoon (1)
  
• 关键词：T ; cadherin ; SNP ; Transcription ; Colorectal cancer
• 刊名：Genes & Genomics
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：36
• 期：3
• 页码：267-274
• 全文大小：
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• 作者单位：Injung Kim (1)
  Jongkeun Park (1)
  Jeong-Ki Kim (1)
  Bong-Kyu Kim (1)
  Hwayoung Lee (1)
  Keonwoo Choi (1)
  Jong-Bok Yoon (2)
  Sungjoo Kim Yoon (1)
  
  1. Department of Medical Lifesciences, The Catholic University of Korea, Seochogu, Banpodong 505, Seoul, 137-701, Republic of Korea
  2. Department of Biochemistry, Yonsei University, Seoul, 120-749, Republic of Korea
  
• ISSN：2092-9293

文摘

T-cadherin is frequently down regulated in various cancers, however, the underlying mechanisms responsible have yet to be elucidated. A genome wide association study of a cohort of Korean adults revealed that the T-cadherin rs3865188 single nucleotide polymorphism (SNP) was associated with serum Adiponectin levels and that its genotypic variants were correlated with risk for colorectal cancer (CRC). To test the function of rs12444338, a SNP tightly linked to the rs3865188 SNP, in T-cadherin transcriptional regulation in colorectal cancer, its effect on transcriptional activity and the capacity of binding activity attributable to allelic variation of the rs12444338 SNP was investigated. An electrophoretic-mobility-shift assay (EMSA) revealed a specific nucleoprotein complex unique to the T allele probe, which displayed lower promoter activity when compared to the G allele. Based on the results of the EMSA using mutant probes, the consensus sequence of the putative transcription factor binding site was determined. Additionally, candidates for putative binding factors to the T allele were also identified. Collectively, the study data suggested that the rs12444338 SNP was involved in transcriptional regulation of T-cadherin gene (CDH13) and that the differential binding of transcription factors at the rs12444338 SNP resulted in altered gene expression. These results elucidate, at least in part, the regulation of T-cadherin expression in CRC and provide further information regarding the effect of nucleotide variation in its promoter region.