Transcriptional regulation of the VEGF gene in dependence of individual genomic variations. Issue 2 (December 2015)

• Record Type: Journal Article
• Authors: Metzger, Carmen S.; Koutsimpelas, Dimitrios; Brieger, Juergen
• Is Part Of: Cytokine. Volume 76:Issue 2(2015)
• Page Start: 519
• Page End: 526
• Publication Date: 2015-12
• Subjects: 3′-UTR 3′-untranslated region -- 5′-UTR 5′-untranslated region -- ARE AU-rich element -- cSNP single nucleotide polymorphisms in coding regions -- HRE hypoxia responsive element -- IRES internal ribosomal entry site -- OSCC oral squamous cell carcinoma -- rSNPs single nucleotide polymorphisms in regulatory regions -- SNP single nucleotide polymorphisms -- sSNP single nucleotide polymorphisms in splicing regions -- TFB transcription factor binding -- TFBS transcription factor binding site -- TSS transcriptional starting site -- VEGF vascular endothelial growth factor; SNP -- Vascular endothelial growth factor -- VEGF -- Review -- Transcriptional regulation; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.07.015
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: VEGF-overexpression is connected to advanced stage and poor survival in cancer. We reviewed a potential influence of VEGF-SNPs on transcriptional regulation. Decreasing binding specificity was observed for MZF1 in presence of +405 C-allele. SNP-2578-linked insertion increased number of potential TFB sites. Association of SNPs and TFB could be an essential part of VEGF-regulation. Abstract: Overexpression of the vascular endothelial growth factor (VEGF) gene has been associated with advanced stage and poor survival in several cancers. The majority of disease-associated VEGF-single nucleotide polymorphisms (SNPs) locate within regulatory regions. Therefore, an influence of SNPs located in the promoter/5′-untranslated region (5′UTR) on transcription factor binding (TFB) and gene expression seems feasible. We reviewed the literature investigating a potential connection of VEGF-SNPs and transcriptional regulation of the VEGF gene. In addition, we employed transcription factor databases to search for VEGF-SNPs which have already been associated with diseases. The objective of this review is to gain an overview about an association of VEGF-SNPs and the transcription factor dependent regulation of the VEGF gene. A decreasing binding specificity of the transcription factor MZF1 in presence of the VEGF-SNP +405 C-allele has been reported. TF databases indicated a potential HIF binding site for the −2578 C-allele representing an important potential inducer of VEGF expression. Additionally, linkage disequilibrium of the −2578 A-allele and an 18 bp insertion increases the number of potential TFB sites. For the VEGF promoter SNP −1154 A/G an interaction with the HRE under participation of the SNP +405 C/G was supposed. The comprehension of the association of specific SNPs and TFB could be an essential part in our understanding of individual differences of VEGF regulation and course of diseases.