title: PADI4 has genetic susceptibility to gastric carcinoma and upregulates CXCR2, KRT14 and TNF-α expression levels.
abstract: 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.
authors.affiliation: Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Yabing
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Emergency Surgery Department of Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.affiliation: Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Pathological Department of Tengzhou People's Central Hospital, Tengzhou, Shandong, P. R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: Clinical Laboratory of PKUCare Luzhong Hospital, Zibo, Shandong, P. R. China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Chang
mesh_terms: D017209:Apoptosis; D001120:Arginine / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002956:Citrulline / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D053547:Keratin-14 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D023063:Receptors, Interleukin-8B; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C507540:KRT14 protein, human; D053547:Keratin-14; D034741:RNA, Small Interfering; D023063:Receptors, Interleukin-8B; D014409:Tumor Necrosis Factor-alpha; D002956:Citrulline; D001120:Arginine; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
keywords: CXCR2; KRT14; TNF-α; peptidyl deiminase (PAD); peptidyl deiminase isoform 4 (PADI4)