- 著者
- Kohanbash Gary Ishikawa Eiichi Fujita Mitsugu Ikeura Maki McKaveney Kayla Zhu Jianzhong Sakaki Masashi Sarkar Saumendra N. Okada Hideho
- 出版者
- Landes Bioscience
- 雑誌
- OncoImmunology (ISSN:21624011)
- 巻号頁・発行日
- vol.1, no.4, pp.487-492, 2012-07
- 被引用文献数
- 10 5
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.