Open AccessA regulatory mutant on TRIM 26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response
Author(s) -
Lyu XiaoMing,
Zhu XiaoWei,
Zhao Manli,
Zuo XianBo,
Huang ZhongXi,
Liu Xiao,
Jiang Tao,
Yang XueXi,
Li Xin,
Long XiaoBing,
Wang JianGuo,
Li JinBang,
Han MingYu,
Wang Shuang,
Liu TengFei,
Zhang Bo,
Sun Tao,
Cheng Zhi,
Qiu MoChang,
Dong Lei,
Zheng Lu,
Zhang LongCheng,
Wang JiaHong,
Wei GanGuan,
Yao Kaitai,
Wang Qian,
Zheng HouFeng,
Li Xin
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1537
Subject(s) - nasopharyngeal carcinoma , biology , chromatin immunoprecipitation , transcription factor , major histocompatibility complex , allele , immune system , microbiology and biotechnology , gene , cancer research , genetics , gene expression , medicine , promoter , radiation therapy
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 .