PADI4 has genetic susceptibility to gastric carcinoma and upregulates CXCR2, KRT14 and TNF-α expression levels.
PADI4 has genetic susceptibility to gastric carcinoma and upregulates CXCR2, KRT14 and TNF-α expression levels.
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PADI4具有胃癌遗传易感性并上调CXCR2、KRT14和TNF-α表达水平
DOI：
10.18632/oncotarget.11398
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发表时间：
2016-09-20
期刊：
影响因子：
--
通讯作者：
Chang X
中科院分区：
文献类型：
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作者：
Zheng Y;Zhao G;Xu B;Liu C;Li C;Zhang X;Chang X
PADI 4（肽基脱亚胺酶同种型4）在许多肿瘤组织中过表达，并将精氨酸残基转化为瓜氨酸残基。该研究使用Illumina SNP微阵列和TaqMan测定来确定PADI 4基因与各种肿瘤风险的可能关联。两种基因分型方法均显示PADI 4基因座中标签SNPs rs 1635566和rs 882537与两个独立队列中的胃癌之间存在显著关联。基于此基因分型结果，我们使用癌通路基因芯片、p53信号转导、信号转导和肿瘤转移PCR阵列来研究PADI 4在胃癌来源的MNK-45细胞中的致瘤通路。我们检测到用抗PADI 4 siRNA处理的MNK-45细胞中CXCR 2、KRT 14和TNF-α的表达水平显著降低。我们还检测到这三个基因在MNK-45细胞中的表达增加，该细胞用过表达PADI 4的pcDNA3.1质粒转染。对于同样来源于胃癌的SGC 7901细胞也获得了高度相似的结果。提示PADI 4基因在胃癌中具有遗传易感性。PADI 4通过上调CXCR 2、KRT 14和TNF-α的表达而促进胃肿瘤的发生，众所周知，CXCR 2、KRT 14和TNF-α激活肿瘤中的血管生成、细胞增殖、细胞迁移和免疫微环境。
PADI4 (peptidyl deiminase isoform 4) is overexpressed in many tumor tissues and converts arginine residues to citrulline residues. This study used an Illumina SNP microarray and a TaqMan assay to determine the possible association of the PADI4 gene with various tumor risks. Both genotyping methods demonstrated significant associations between the tag SNPs rs1635566 and rs882537 in the PADI4 locus with gastric carcinoma in two independent cohorts. Based on this genotyping result, we used the Cancer Pathway Finder, p53 Signaling, Signal Transduction and Tumor Metastasis PCR arrays to investigate the tumorigenic pathway of PADI4 in MNK-45 cells derived from gastric carcinoma. We detected significantly decreased expression levels of CXCR2, KRT14 and TNF-α in MNK-45 cells that were treated with anti-PADI4 siRNA. We also detected increased expression of these three genes in MNK-45 cells transfected with a pcDNA3.1 plasmid overexpressing PADI4. A highly similar result was also obtained for SGC 7901 cells, which also originate from gastric carcinoma. Our result indicates that the PADI4 gene has genetic susceptibility in gastric carcinoma. PADI4 contributes to gastric tumorigenesis by upregulating CXCR2, KRT14 and TNF-α expression, which are well known to activate angiogenesis, cell proliferation, cell migration and the immune microenvironment in tumors.