alexa Regulation of VEGF-A Expression in Endothelial Cells by Transcriptional Gene Activation or Transcriptional Gene Silencing: Analysis of Genome Wide Transcriptional Response

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Regulation of VEGF-A Expression in Endothelial Cells by Transcriptional Gene Activation or Transcriptional Gene Silencing: Analysis of Genome Wide Transcriptional Response

Vascular endothelial growth factor (VEGF-A) is a key regulator of angiogenesis in many diseases, such as cancer and cardiovascular diseases . For that reason it is not surprising that its effects on endothelial cells have been studied by several approaches, such as microarray analysis  and next generation sequencing . For example, Shin et al. used microarray analysis to study transcriptional response to human dermal lymphatic endothelial cells treated with recombinant human VEGF-A165 . For the inhibition of VEGF/ VEGFR signaling, Bevacizumab has been used in a mouse xenograft model of endometrial cancer . However, manipulation of VEGF-A expression, either upregulating the expression by delivering VEGF-A expression cassettes and recombinant proteins or inhibiting it by using RNAi or antibodies, is somewhat artificial in terms of endothelial biology. Recently it has become evident that small RNAs, such as miRNA, siRNA or shRNA, can regulate target gene expression via promoter targeted epigenetic modifications . These processes have been studied in plants for a long time, but when Morris et al.  found that small RNAs directed to the gene promoters induce transcriptional gene silencing (TGS) and a little later Li et al. showed that they can also induce transcriptional gene activation (TGA), their potential as therapeutics was quickly realized. However, the specificity and safety of these promoter targeted small RNAs must be evaluated before clinical trials.

 
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