In:
Cancer Medicine, Wiley, Vol. 7, No. 8 ( 2018-08), p. 3848-3861
Abstract:
The major histocompatibility complex ( MHC ) is most closely associated with nasopharyngeal carcinoma ( NPC ), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two‐stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT ‐ PCR analysis ( qRT ‐ PCR ) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal ( NP ) samples. Luciferase reporter assay and chromatin immunoprecipitation (Ch IP ) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM 26 displayed the strongest association ( OR = 1.909, Pcombined = 2.750 × 10 −19 ). We also observed that TRIM 26 was significantly downregulated in NPC tissue samples with genotype AA / AT than TT . Immunohistochemistry ( IHC ) test also found the TRIM 26 protein expression in NPC tissue samples with the genotype AA / AT was lower than TT . According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 ( YY 1). We observed that the luciferase activity of YY 1 which is binding to the A allele of rs117565607 was suppressed. Ch IP data showed that YY 1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM 26 downregulation was related to low immune response in NPC . We have identified a novel gene TRIM 26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM 26 downregulation and low immune response in NPC .
Type of Medium:
Online Resource
ISSN:
2045-7634
,
2045-7634
DOI:
10.1002/cam4.2018.7.issue-8
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2659751-2
