Cargando…
Proteome-Wide Alterations of Asymmetric Arginine Dimethylation Associated With Pancreatic Ductal Adenocarcinoma Pathogenesis
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)-conta...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744470/ https://www.ncbi.nlm.nih.gov/pubmed/33344439 http://dx.doi.org/10.3389/fcell.2020.545934 |
_version_ | 1783624426958356480 |
---|---|
author | Wei, Meijin Tan, Chaochao Tang, Zhouqin Lian, Yingying Huang, Ying Chen, Yi Chen, Congwei Zhou, Wen Cai, Tao Hu, Jiliang |
author_facet | Wei, Meijin Tan, Chaochao Tang, Zhouqin Lian, Yingying Huang, Ying Chen, Yi Chen, Congwei Zhou, Wen Cai, Tao Hu, Jiliang |
author_sort | Wei, Meijin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7744470 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77444702020-12-18 Proteome-Wide Alterations of Asymmetric Arginine Dimethylation Associated With Pancreatic Ductal Adenocarcinoma Pathogenesis Wei, Meijin Tan, Chaochao Tang, Zhouqin Lian, Yingying Huang, Ying Chen, Yi Chen, Congwei Zhou, Wen Cai, Tao Hu, Jiliang Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2020-12-03 /pmc/articles/PMC7744470/ /pubmed/33344439 http://dx.doi.org/10.3389/fcell.2020.545934 Text en Copyright © 2020 Wei, Tan, Tang, Lian, Huang, Chen, Chen, Zhou, Cai and Hu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Wei, Meijin Tan, Chaochao Tang, Zhouqin Lian, Yingying Huang, Ying Chen, Yi Chen, Congwei Zhou, Wen Cai, Tao Hu, Jiliang Proteome-Wide Alterations of Asymmetric Arginine Dimethylation Associated With Pancreatic Ductal Adenocarcinoma Pathogenesis |
title | Proteome-Wide Alterations of Asymmetric Arginine Dimethylation Associated With Pancreatic Ductal Adenocarcinoma Pathogenesis |
title_full | Proteome-Wide Alterations of Asymmetric Arginine Dimethylation Associated With Pancreatic Ductal Adenocarcinoma Pathogenesis |
title_fullStr | Proteome-Wide Alterations of Asymmetric Arginine Dimethylation Associated With Pancreatic Ductal Adenocarcinoma Pathogenesis |
title_full_unstemmed | Proteome-Wide Alterations of Asymmetric Arginine Dimethylation Associated With Pancreatic Ductal Adenocarcinoma Pathogenesis |
title_short | Proteome-Wide Alterations of Asymmetric Arginine Dimethylation Associated With Pancreatic Ductal Adenocarcinoma Pathogenesis |
title_sort | proteome-wide alterations of asymmetric arginine dimethylation associated with pancreatic ductal adenocarcinoma pathogenesis |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744470/ https://www.ncbi.nlm.nih.gov/pubmed/33344439 http://dx.doi.org/10.3389/fcell.2020.545934 |
work_keys_str_mv | AT weimeijin proteomewidealterationsofasymmetricargininedimethylationassociatedwithpancreaticductaladenocarcinomapathogenesis AT tanchaochao proteomewidealterationsofasymmetricargininedimethylationassociatedwithpancreaticductaladenocarcinomapathogenesis AT tangzhouqin proteomewidealterationsofasymmetricargininedimethylationassociatedwithpancreaticductaladenocarcinomapathogenesis AT lianyingying proteomewidealterationsofasymmetricargininedimethylationassociatedwithpancreaticductaladenocarcinomapathogenesis AT huangying proteomewidealterationsofasymmetricargininedimethylationassociatedwithpancreaticductaladenocarcinomapathogenesis AT chenyi proteomewidealterationsofasymmetricargininedimethylationassociatedwithpancreaticductaladenocarcinomapathogenesis AT chencongwei proteomewidealterationsofasymmetricargininedimethylationassociatedwithpancreaticductaladenocarcinomapathogenesis AT zhouwen proteomewidealterationsofasymmetricargininedimethylationassociatedwithpancreaticductaladenocarcinomapathogenesis AT caitao proteomewidealterationsofasymmetricargininedimethylationassociatedwithpancreaticductaladenocarcinomapathogenesis AT hujiliang proteomewidealterationsofasymmetricargininedimethylationassociatedwithpancreaticductaladenocarcinomapathogenesis |