PADI2 gene confers susceptibility to breast cancer and plays tumorigenic role via ACSL4, BINC3 and CA9 signaling.
PADI2 gene confers susceptibility to breast cancer and plays tumorigenic role via ACSL4, BINC3 and CA9 signaling.
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PADI2 基因赋予乳腺癌易感性，并通过 ACSL4、BINC3 和 CA9 信号传导发挥致瘤作用
DOI：
10.1186/s12935-016-0335-0
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发表时间：
2016
影响因子：
5.8
通讯作者：
Chang X
中科院分区：
文献类型：
--
作者：
Wang H;Xu B;Zhang X;Zheng Y;Zhao Y;Chang X
背景肽基精氨酸脱亚胺酶（PAD）是一种将精氨酸残基后转化为瓜氨酸残基的酶。最近的研究表明，PADI 2（PAD同种型2），PAD家族的成员，参与了一些肿瘤，特别是乳腺癌的致瘤过程。然而，关于PADI 2在肿瘤发生中的机制知之甚少。本研究旨在阐明PADI 2在乳腺肿瘤中的致瘤作用及其调控途径。方法采用Sequenom MassARRAY和TaqMan基因分型方法，研究PADI 2基因SNPs与乳腺肿瘤风险的相关性。进行PCR阵列分析，包括癌症通路发现器和信号转导PCR阵列，以研究用抗PADI 2 siRNA处理后MCF-7乳腺癌细胞系中PADI 2的致瘤通路。采用细胞增殖、凋亡和细胞迁移实验观察PADI 2对MCF-7细胞增殖、凋亡和迁移的影响。结果Sequenom MassARRAY和TaqMan基因分型实验均证实PADI 2基因中的SNP rs 10788656与乳腺癌显著相关。实时荧光定量PCR结果显示，抑制PADI 2表达可显著增加MCF-7细胞中CA 9的表达，降低ACSL 4和BIRC 3的表达。抑制PADI 2的表达也显着降低了MCF-7细胞的迁移能力，但不影响细胞增殖或凋亡。PADI 2表达有助于乳腺肿瘤细胞的异常迁移。PADI 2通过调节ACSL 4、BINC 3和CA 9的表达来影响乳腺肿瘤细胞中的肿瘤发生，已知ACSL 4、BINC 3和CA 9促进异常脂质代谢和肿瘤的细胞侵袭。
BackgroundPeptidylarginine deiminase (PAD) post-translationally converts arginine residues to citrulline residues. Recent studies have suggested that PADI2 (PAD isoform 2), a member of the PAD family, is involved in the tumorigenic process of some tumors, especially breast cancer. However, little is known about the mechanisms of PADI2 in tumorigenesis. This study aimed to elucidate the tumorigenic role and regulatory pathway of PADI2 in breast tumors.MethodsThe Sequenom MassARRAY and TaqMan genotyping methods were used to investigate the correlation between PADI2 gene SNPs and various tumor risks. PCR array analyses, including cancer pathway finder and signal transduction PCR arrays, were performed to investigate the tumorigenic pathway of PADI2 in the MCF-7 breast cancer cell line following treatment with anti-PADI2 siRNA. Cell proliferation, apoptosis and transwell migration assays were performed to observe the effect of PADI2 in MCF-7 cells treated with anti-PADI2 siRNA.ResultsBoth Sequenom MassARRAY and TaqMan genotyping assays demonstrated that SNP rs10788656 in the PADI2 gene was significantly associated with breast cancer. PCR arrays indicated that inhibiting PADI2 expression significantly increased expression of CA9 and decreased expression of ACSL4 and BIRC3 in MCF-7 cells, which was verified using real-time PCR. Inhibiting PADI2 expression also significantly decreased the migration ability of MCF-7 cells but did not affect cell proliferation or apoptosis.ConclusionsThe PADI2 gene confers susceptibility to breast cancer. PADI2 expression contributes to abnormal migration of breast tumor cells. PADI2 affects tumorigenesis in breast tumor cells by regulating the expression of ACSL4, BINC3 and CA9, which are known to promote abnormal lipid metabolism and cell invasion of tumors.