PADI1通过激活ERK1/2-p38信号通路促进胰腺癌中的上皮-间质转化。
PADI1 contributes to EMT in PAAD by activating the ERK1/2-p38 signaling pathway.
作者信息
Ji Tengfei, Ma Keqiang, Chen Liang, Cao Tiansheng
机构信息
Department of Hepatobiliary Surgery, Affiliated Huadu Hospital, Southern Medical University (People's Hospital of Huadu District), Guangzhou, China.
出版信息
J Gastrointest Oncol. 2021 Jun;12(3):1180-1190. doi: 10.21037/jgo-21-283.
BACKGROUND
Peptidylarginine deiminase 1 (PADI1) has been reported to promote tumorigenesis in breast cancer. However, the functional role of PADI1 in pancreatic ductal adenocarcinoma (PAAD) has remained elusive until now.
METHODS
The expression pattern of PADI1 in PAAD tissues and normal tissues was analyzed using The Cancer Genome Atlas (TCGA) dataset. A Kaplan-Meier curve analysis was performed to evaluate the prognostic value of PADI1 in PAAD patients. PADI1 was knocked down in CFPAN-1 and HPAC cells, and overexpressed in PANC-1 and Bxpc-3 cells by RNA interference. A wound-healing assay was performed to analyze relative cell migration distance. Cell migration and invasion were assessed by a Transwell assay. Related protein expression levels were measured by western blot and immunofluorescence.
RESULTS
The bioinformatics analysis showed that PADI1 was overexpressed in PAAD tissues and associated with a poor survival prognosis. The knockdown of PADI1 suppressed cell migration and invasion, and activated the ERK1/2-p38 signaling pathway in CFPAN-1 and HPAC cells. The overexpression of PADI1 produced the opposite results in PANC-1 and Bxpc-3 cells. Additionally, treatment with an MEK1/2 inhibitor significantly attenuated the effects of PADI1 knockdown on cell migration, invasion, the epithelial-mesenchymal transition (EMT) process, and p-ERK1/2 and p38 expression in CFPAN-1 and HPAC cells.
CONCLUSIONS
Our data suggested that PADI1 may function as an oncogene in regulating metastasis in PAAD.
背景
据报道，肽基精氨酸脱亚氨酶1（PADI1）可促进乳腺癌的肿瘤发生。然而，迄今为止，PADI1在胰腺导管腺癌（PAAD）中的功能作用仍不清楚。
方法
使用癌症基因组图谱（TCGA）数据集分析PADI1在PAAD组织和正常组织中的表达模式。进行Kaplan-Meier曲线分析以评估PADI1在PAAD患者中的预后价值。通过RNA干扰在CFPAN-1和HPAC细胞中敲低PADI1，并在PANC-1和Bxpc-3细胞中过表达。进行伤口愈合试验以分析相对细胞迁移距离。通过Transwell试验评估细胞迁移和侵袭。通过蛋白质免疫印迹和免疫荧光测量相关蛋白表达水平。
结果
生物信息学分析表明，PADI1在PAAD组织中过表达，并与不良生存预后相关。敲低PADI1可抑制CFPAN-1和HPAC细胞的迁移和侵袭，并激活ERK1/2-p38信号通路。PADI1的过表达在PANC-1和Bxpc-3细胞中产生相反的结果。此外，用MEK1/2抑制剂处理可显著减弱PADI1敲低对CFPAN-1和HPAC细胞的迁移、侵袭、上皮-间质转化（EMT）过程以及p-ERK1/2和p38表达的影响。
结论
我们的数据表明，PADI1可能作为一种癌基因在PAAD的转移调节中发挥作用。
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