Investigating the pathogenic role of PADI4 in oesophageal cancer.
Investigating the pathogenic role of PADI4 in oesophageal cancer.
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DOI：
10.7150/ijbs.7.769
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发表时间：
2011
影响因子：
9.2
通讯作者：
Han J
中科院分区：
文献类型：
--
作者：
Chang X;Hou X;Pan J;Fang K;Wang L;Han J
PADI 4在免疫后将肽基精氨酸转化为瓜氨酸。PADI 4可通过p53靶基因启动子中组蛋白H3的瓜氨酸化作用破坏凋亡过程。本研究采用免疫组化、Western blotting和真实的时间PCR检测PADI 4在不同亚型食管癌中的表达。本研究还研究了胆汁酸脱氧胆酸盐（DCA）对来源于EC的Eca-109细胞中PADI 4表达的影响。采用TUNEL法、MTT法和流式细胞术检测细胞凋亡和DCA诱导的细胞毒性。此外，本研究还采用Illumina GoldenGate分析法，探讨了中国人群PADI 4基因单核苷酸多态性（SNP）与食管癌风险的相关性。与癌旁组织相比，食管鳞状细胞癌（ESCC，n=9）和食管腺癌（EAC，n=5）组织中PADI 4的转录和翻译水平显著升高。免疫组化法检测PADI 4在食管鳞癌（98.56%，n=139）、EAC（87.5%，n=16）和食管小细胞未分化癌（91.7%，n=12）中的表达，而在正常组织中无表达（0%，n=16）。此外，PADI 4水平与ESCC的病理分类正相关（p=0.009）。PADI 4表达水平与诱导的Eca-109细胞中凋亡细胞的数量一致。rs 10437048 [OR= 0.012831; 95% CI，0.001746~0.094278; p=1.556×10-12]与EC风险降低显著相关，而rs 41265997 [OR=12.7; 95% CI，0.857077~33.207214; p=3.896×10-8]与EC风险增加显著相关。PADI 4基因外显子3中的rs 41265997是非同义的，并将ACG转化为ATG，导致蛋白质274位的苏氨酸/甲硫氨酸转化。携带rs 2501796和rs 2477134变异等位基因的单倍型GC与EC风险增加显著相关（频率=0.085，p=0.0256，OR=2.7）。提示PADI 4的表达与EC的致瘤过程及DCA诱导的细胞凋亡有关。PADI 4基因可能是一个有效的EC易感基因。
PADI4 post-translationally converts peptidylarginine to citrulline. PADI4 can disrupt the apoptotic process via the citrullination of histone H3 in the promoter of p53-target genes. The current study focused on PADI4 expression in various subtypes of oesophageal carcinoma (EC) by immunohistochemistry, western blotting and real time PCR. The study also investigated the effect of bile acid deoxycholate (DCA) on PADI4 expression in Eca-109 cells that originated from EC. Apoptosis and DCA-induced toxicity were analyzed by TUNEL, MTT assay and flow cytometry. Additionally, the present study investigated the correlation between single nucleotide polymorphism (SNP) in PADI4 gene and EC risk in Chinese population using Illumina GoldenGate assay. Compared with paraneoplastic tissues, the transcriptional and translational levels of PADI4 were significantly elevated in oesophageal squamous cell carcinoma (ESCC, n=9) and oesophageal adenocarcinoma (EAC, n=5) tissues. Immunolabeling detected expression of PADI4 in ESCC tissues (98.56%, n=139), EAC samples (87.5%, n=16) and oesophageal small cell undifferentiated carcinoma (91.7%, n=12) but not in normal tissues (0%, n=16). Furthermore, PADI4 levels is positively correlated with the pathological classification of ESCC (p=0.009). PADI4 expression levels were consistent with the number of apoptotic cells in the induced Eca-109 cells. rs10437048 [OR= 0.012831; 95% CI, 0.001746~0.094278; p=1.556×10-12] were significantly associated with decreased risk of EC, whereas rs41265997 [OR=12.7; 95% CI, 0.857077~33.207214; p=3.896×10-8] were significantly associated with increased risk of EC. rs41265997 in exon 3 of PADI4 gene is non-synonymous and converts ACG to ATG resulting in a threonine /methionine conversion at position 274 of the protein. Haplotypes GC that carries the variant alleles for rs2501796 and rs2477134 was significantly associated with increased risk of EC (frequency=0.085, p=0.0256, OR=2.7). The results suggest that PADI4 expression is related to the tumorigenic process of EC and the DCA-induced apoptosis. The PADI4 gene may be a valid EC susceptibility gene.
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影响因子：
3.8
作者：
Looby E;Abdel-Latif MM;Athié-Morales V;Duggan S;Long A;Kelleher D
通讯作者：
Kelleher D
影响因子：
3.8
作者：
Chang X;Han J;Pang L;Zhao Y;Yang Y;Shen Z
通讯作者：
Shen Z
影响因子：
5.3
作者：
Li, Pingxin;Yao, Hongjie;Wang, Yanming
通讯作者：
Wang, Yanming
影响因子：
11.2
作者：
Tanikawa, Chizu;Ueda, Koji;Matsuda, Koichi
通讯作者：
Matsuda, Koichi
影响因子：
7.2
作者：
Liu, GY;Liao, YF;Hung, HC
通讯作者：
Hung, HC