XAGE-1b(X antigen family member 1B)属于XAGE亚家族,是一种肿瘤-睾丸抗原(cancer/testis antigen,CTA),表达于正常人睾丸组织和多种类型的肿瘤细胞中.本实验室前期研究发现,该基因在涎腺腺样囊性癌高转移细胞系中呈高表达.为了进一步研究XAGE-1b下游调控基因,本实验采用ChIP-Seq技术筛查XAGE-1b蛋白质可能存在的DNA结合片段.结果发现,XAGE-1b下游调控基因富集于细胞分裂(cell division,P-Value=7.95e-04)、细胞周期调控(cell cycle,P-Value=5.532e-03)、及癌症相关基因(GESA/MSigDB module_11,P-Value=2.010e-06)中.同时发现,XAGE-1b下游调控多个基因的表达产物(NCBI/interactions 22827,P-Value=4.678e-06)能与原癌基因c-Myc的启动子抑制蛋白PUF60发生蛋白质相互作用,并通过qPCR进行了验证.这些研究对阐明XAGE-1b在肿瘤细胞的增殖和转移中的作用有重要意义.
XAGE-lb is a cancer/testis antigen and belongs to XAGE subfamily. XAGE-1b protein was found in testis and varieties of tumor tissues. Our previous study found the expression of XAGE-1b in the high metastatic cell line of adenoid cystic carcinoma of salivary gland is significantly higher than in low metastatic cell line. In this study, we profiled the genome-wide DNA binding sites of XAGE-1b by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) on Illumina HiSeq 2000 platform. The downstream genes were indentified and was found highly enriched in cell division(P- Value = 7. 95e-04), cell cycle (P-Value = 5. 532e-03 ) in GOSlim analysis and in cancer modules (GESA/MSigDB module 11, P-Value = 2. 010e-06) in HOMER analysis. The result also relvealed that XAGE-1 b protein regulates c-Myc indirectly by promoter repressor protein PUF60 binding proteins such as PABPC1. It proposed that XAGE-lb may play an important role in metastatic, proliferation and tumorigenesis through e-Myc-dependent pathway.