PADI1 contributes to EMT in PAAD by activating the ERK1/2-p38 signaling pathway.

Abstract

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 vitro in PAAD.

• Authors: Tengfei Ji, Keqiang Ma, Liang Chen, Tiansheng Cao
• Journal: Journal of gastrointestinal oncology (J Gastrointest Oncol) Vol. 12 Issue 3 Pg. 1180-1190 (Jun 2021) ISSN: 2078-6891 [Print] China
• PMID: 34295566 (Publication Type: Journal Article)
• Copyright: 2021 Journal of Gastrointestinal Oncology. All rights reserved.