Association of rs4073 with IL-8 activation by transcription factor and its role in angiogenesis, diffusion of immature white blood cell and acute lymphoblastic leukemia by bioinformatics analysis

Introduction & Objectives: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Recent studies have identified the genetic susceptibility value of SNPs for cancer risk. IL-8 releases immature white blood cells into the blood. Overexpression of IL-8 also causes angiogenesis and metastasis in cancer tumor. Rs4073 is a polymorphism in the IL-8 promoter locus. Polymorphisms at the promoter site affect gene expression by interaction of SNP with transcription factors. The purpose of this study was to investigate the activation of IL-8 by GR transcription factors between individuals with T and A alleles at rs4073, when hsa-miR-let-7a-2-3p inhibits NR3C1 transcription factor.Materials & Methods: Firstly, the transcription factors of the gene was predicted by the PROMO promoter database. The miRWalk2 database was used to identify IL-8-related microRNAs and let-7a-2-3p hsa-miR- was selected. Information of hsa-miR-let-7a-2-3P was obtained from miRbase database. The target gene of this microRNA was identified by using miRNASNPV2 database. The associated signal pathway was identified using the DAVID and KEGG databases.Results: Results from the PROMO promoter databases showed that the presence of the T allele causes binding of the GR-bata transcription factor at this site and this transcription factor doesnt bind in the presence of the A allele. Prediction by the miRNASNP V2 database showed that the target of hsa-miR-let-7a-2-3p is the GR-beta gene (NR3C1).Conclusion: According to the data obtained, it was predicted that hsa-miR-let-7a-2-3p might decrease GR-beta expression and that the Interleukin-8 gene would be less activated by the GR-beta transcription factor. However, despite suppression of transcription factor, it is expected that in pepole with the T allele that have more binding site for the GR transcription factor, the GR transcription factor will activate the IL-8 gene. Finally, studies suggested that increased risk of angiogenesis as well as the release of immature white blood cells into the bloods would increase IL-8 activation in people with T alleles.

کلیدواژه ها:

acute lymphoblastic leukemia ، SNP ، IL-8 ، hsa-miR-let-7a-2-3p