Arginine methylation catalyzed by
protein arginine methyltransferases (PRMTs) performs essential roles in regulating
cancer initiation and progression, but its implication in pancreatic ductal
adenocarcinoma (PDAC) requires further elucidation. In this study,
asymmetric dimethylarginine (ADMA)-containing
peptides in PDAC cell line PANC-1 were identified by label-free quantitative proteomics combined with affinity purification, using human non-cancerous pancreatic ductal epithelium cell line HPDE6c7 as the control. In total, 289 ADMA sites in 201
proteins were identified in HPDE6c7 and PANC-1 cells, including 82 sites with lower dimethylation and 37 sites with higher dimethylation in PANC-1 cells compared with HPDE6c7 cells. These ADMA-containing
peptides demonstrated significant enrichment of
glycine and
proline residues in both cell lines. Importantly,
leucine residues were significantly enriched in ADMA-containing
peptides identified only in HPDE6c7 cells or showing lower dimethylation in PANC-1 cells. ADMA-containing
proteins were significantly enriched in multiple biological processes and signaling cascades associated with
cancer development, such as spliceosome machinery, the Wnt/β-
catenin, Hedgehog,
tumor growth factor beta (TGF-β), and
mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, PDAC cell lines with enhanced cell viability showed lower
PRMT4 protein abundance and global ADMA-containing
protein levels compared with HPDE6c7. PRMT4 overexpression partially recovered ADMA-containing
protein levels and repressed viability in PANC-1 cells. These results revealed significantly altered ADMA-containing
protein profiles in human
pancreatic carcinoma cells, which provided a basis for elucidating the pathogenic roles of PRMT-mediated
protein methylation in
pancreatic cancer.