机构：[1]Department of laboratory medicine, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China[2]Shenzhen Key Laboratory of Viral Oncology, the Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, China[3]Zhujiang Hospital, Southern Medical University, Guangzhou, China[4]Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Westlake University, Hangzhou, Zhejiang, China[5]Institute of Aging Research and the Affiliated Hospital, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China[6]School of Life Sciences, Fudan University, Shanghai, China[7]Department of Pathology, School of Medicine, The Children Hospital of Zhejiang University, Hangzhou, China[8]Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China[9]Cancer Research Institute and the Provincial Key Laboratory of Functional Proteomics, Southern Medical University, Guangzhou, China[10]Beijing Genome Institute (BGI), Shenzhen, China[11]School of Biotechnology of Southern Medical University, Guangzhou, China[12]Clinical Laboratory, Nanfang Hospital of Southern Medical University, Guangzhou, China[13]Department of Otolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China[14]Department of Pathology, Qingyuan People’s Hospital, Qingyuan, China[15]School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland[16]Department of Pathology, Nanfang Hospital of Southern Medical University, Guangzhou, China[17]The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China[18]Suzhou Science& Technology Town Hospital, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China[19]Jiangxi Medical College, Shangrao, Jiangxi, China[20]School of Life Science, Beijing Institute of Technology, Beijing, China[21]Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China[22]Department of Otolaryngology-Head and Neck Surgery, 303 Hospital of People’s Liberation Army of China, Nanning, China
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 (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 x 10(-19)). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 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 I (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.
基金：
This study was supported by the
National Natural Science Foundation of
China (No. 30371535, No. 81572644
and No. 81502335), the Science and
Technology Project of Shenzhen
(JCYJ20170413165531148), China
Postdoctoral Science Foundation
(No. 2016M602493), Science and
Technology Program of Guangzhou,
China (No. 201704020127), Sanming
Project of Medicine in Shenzhen
(Academician Kaitai Yao’s Group For
Nasopharyngeal Carcinoma Research
from Southern Medical University)
(No. SZSM201612023). In addition,
we appreciate Dr. Xin-qiang
Rao, from
CapitalBio Corporation, Beijing, China, for
his designing primers for high-resolution
DNA melting analysis (HRM) in this study.
We would like to appreciate the National
Natural Science Foundation of China (No.
81501145), the Zhejiang Provincial Natural
Science Foundation for Distinguished
Young Scholars of China (LR17H070001),
the State Key Development Program for
Basic Research of China (973 Program,
2014CB541701), and the “Thousand
Talents” Program.
第一作者机构：[1]Department of laboratory medicine, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China[2]Shenzhen Key Laboratory of Viral Oncology, the Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, China[3]Zhujiang Hospital, Southern Medical University, Guangzhou, China
共同第一作者：
通讯作者：
通讯机构：[*1]Shenzhen Hospital, Southern Medical University, Shenzhen, China.[*2]Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Westlake University, Hangzhou, Zhejiang, China.[*3]Zhujiang Hospital, Southern Medical University, Guangzhou, China
推荐引用方式(GB/T 7714)：
Xiao-Ming Lyu,Xiao-Wei Zhu,Manli Zhao,et al.A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response[J].CANCER MEDICINE.2018,7(8):3848-3861.doi:10.1002/cam4.1537.
APA：
Xiao-Ming Lyu,Xiao-Wei Zhu,Manli Zhao,Xian-Bo Zuo,Zhong-Xi Huang...&Xin Li.(2018).A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response.CANCER MEDICINE,7,(8)
MLA：
Xiao-Ming Lyu,et al."A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response".CANCER MEDICINE 7..8(2018):3848-3861
