Frontiers in Immunology (Mar 2023)

Identification of cuproptosis hub genes contributing to the immune microenvironment in ulcerative colitis using bioinformatic analysis and experimental verification

  • Cejun Yang,
  • Cejun Yang,
  • Wendi Wang,
  • Sang Li,
  • Zhengkang Qiao,
  • Xiaoqian Ma,
  • Xiaoqian Ma,
  • Min Yang,
  • Min Yang,
  • Juan Zhang,
  • Juan Zhang,
  • Lu Cao,
  • Lu Cao,
  • Shanhu Yao,
  • Shanhu Yao,
  • Zhe Yang,
  • Wei Wang,
  • Wei Wang

DOI
https://doi.org/10.3389/fimmu.2023.1113385
Journal volume & issue
Vol. 14

Abstract

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InstructionUlcerative colitis (UC) can cause a variety of immune-mediated intestinal dysfunctions and is a significant model of inflammatory bowel disease (IBD). Colorectal cancer (CRC) mostly occurs in patients with ulcerative colitis. Cuproptosis is a type of procedural death that is associated with different types of diseases to various degrees.MethodsWe used a combination of bioinformatic prediction and experimental verification to study the correlation between copper poisoning and UC. We used the Gene Expression Omnibus database to obtain disease gene expression data and then identified relevant genes involved in various expression levels in normal and UC samples. The Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed to cluster the genes that are highly responsible and find the central interaction in gene crosstalk. Notably, DLD, DLAT, and PDHA1 were present in high-scoring PPI networks. In addition, hub gene expression information in UC tissues was integrated to estimate the relationship between UC copper poisoning and the immune environment.ResultsIn our study, the expression of DLD, DLAT, and PDHA1 in UC tissues was lower than that in normal tissues. The key genes associated with cuproptosis have therapeutic effects on immune infiltration. We verified the expression of DLD, DLAT, and PDHA1 using real-time quantitative polymerase chain reaction in mouse models of UC induced by DSS.DiscussionNotably, this study clearly indicates that bioinformatic analysis performed to verify the experimental methods provides evidence that cuproptosis is associated with UC. This finding suggests that immune cell infiltration in UC patients is associated with cuproptosis. The key genes associated with cuproptosis can be helpful for discovering the molecular mechanism of UC, thus facilitating the improvement of UC treatment and preventing the associated CRC.

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