title: Differential activity of interferon-α8 promoter is regulated by Oct-1 and a SNP that dictates prognosis of glioma.
abstract: We have previously reported that the single nucleotide polymorphism (SNP) rs12553612 in IFNA8 is associated with better overall survival of glioma patients with the AA-genotype compared with patients with the AC-genotype. As rs12553612 is located in the IFNA8 promoter, we hypothesized that the A-allele allows for an enhanced IFNA8 promoter activity compared with the C-allele. Reporter assays in the human monocyte derived THP-1 cell line demonstrated a superior promoter activity of the A-allele compared with the C-allele. Electrophoretic mobility shift assays (EMSA) further demonstrated that the A-genotype specifically binds to more nuclear proteins than the C-genotype, including the transcription factor Oct-1. Further, co-transfection of plasmids encoding Oct-1 and the reporter constructs revealed that Oct-1 enhanced the promoter activity with the A- but not the C-allele. Taken together, our data demonstrate that the A-allele in the rs12553612 SNP, which is associated with better glioma patient survival, allows for IFNA8 transcription by allowing for Oct-1 binding, which is absent in patients with C allele, and suggests a molecular mechanism of IFNA8 mediated immune-surveillance of glioma progression.
authors: Brain Tumor Program; University of Pittsburgh Cancer Institute; Pittsburgh, PA USA ; Infectious Diseases and Microbiology; University of Pittsburgh Graduate School of Public Health; Pittsburgh, PA USA.
authors: Gary
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authors: Kohanbash
authors: Eiichi
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authors: Ishikawa
authors: Mitsugu
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authors: Fujita
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authors: Ikeura
authors: Kayla
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authors: McKaveney
authors: Jianzhong
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authors: Zhu
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authors: Saumendra N
authors: SN
authors: Sarkar
authors: Hideho
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authors: Okada