Differential expression of lysine acetylation proteins in gastric cancer treated with a new antitumor agent bioactive peptide chelate selenium

PeerJ. 2023 Jan 17:11:e14384. doi: 10.7717/peerj.14384. eCollection 2023.

Abstract

The method of anticancer bioactive peptide (ACBP) functionalized selenium particle (Se), which has enhanced anticancer activity, inhibited the growth of gastric cancer (GC) cells, and increased the ability of apoptosis in vitro, has been reported in previous studies. We used tandem mass spectrometry (TMT) labeling to construct a complete atlas of the acetylation-modified proteome in GC MKN-45 cells treated with ACBP-Se. The proteomics data database was searched and analyzed by bioinformatics: Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), functional enrichment, and protein-protein interaction network. Finally, we conducted a quantitative PRM analysis of the selected target-modified peptides. We identified 4,958 acetylation sites from 1,926 proteins in this research. Among these, 4,467 acetylation sites corresponding to 1,777 proteins were quantified. Based on the above data and standards, we found that in the ACBP-Se group vs. the control group, 297 sites were upregulated, and 665 sites were downregulated. We systematically assessed the proteins containing quantitative information sites, including protein annotation, functional classification, and functional enrichment, cluster analysis supported by functional enrichment, domain structures, and protein interaction networks. Finally, we evaluated differentially expressed lysine acetylation sites. We revealed that SHMT2 K200 and PGK1 K97 were the most critical acetylated non-histone proteins, which may have an essential role in ACBP-Se treatment. Here, we identified and quantified the lysine acetylation proteins in GC cells treated with ACBP-Se. The characterization of acetylation indicates that acetylated proteins might be pivotal in the biological process, molecular binding, and metabolic pathways of ACBP-Se treatment progress. Our findings provide a broad understanding of acetylation ACBP-Se treatment of GC, suggesting a potential application for molecular targeted therapy.

Keywords: Acetylation; Anticancer bioactive peptides; Gastric cancer; Selenium.

MeSH terms

  • Acetylation
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Humans
  • Lysine / pharmacology
  • Peptides / pharmacology
  • Proteome / metabolism
  • Selenium* / pharmacology
  • Selenium* / therapeutic use
  • Stomach Neoplasms* / drug therapy

Substances

  • Antineoplastic Agents
  • Lysine
  • Peptides
  • Proteome
  • Selenium

Grants and funding

This work was supported by grant from the National Natural Science Foundation of China (grant no. 81960560) and the Foundation of Inner Mongolia Science and Technology Achievement Transformation (grant no. CGZH2018149), the Natural Science Foundation of Inner Mongolia (grant nos. 2021BS08011 and 2021LHMS08045), Innovation and entrepreneurship training program for college students of Inner Mongolia Medical University (grant no. 202210132025), Laboratory Open Fund Project of Inner Mongolia Medical University (grant no. 2022ZN13), and the Scientific research project of Inner Mongolia Medical University (grant no. YKD2022MS027). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.