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

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

doi:10.3389/fimmu.2023.1113385

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

Front Immunol. 2023 Mar 7:14:1113385. doi: 10.3389/fimmu.2023.1113385. eCollection 2023.

Authors

Cejun Yang^{1

2}, Wendi Wang³, Sang Li⁴, Zhengkang Qiao³, Xiaoqian Ma^{1

2}, Min Yang^{1

2}, Juan Zhang^{1

2}, Lu Cao^{1

2}, Shanhu Yao^{1

2}, Zhe Yang³, Wei Wang^{1

2}

Affiliations

¹ The Institute for Cell Transplantation and Gene Therapy, The Third Xiangya Hospital of Central South University, Changsha, China.
² Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, China.
³ College of Life Science, Liaoning University, Shenyang, China.
⁴ Department of Research, Engineering and Technology Research Center for Xenotransplantation of Human Province, Changsha, China.

Abstract

Instruction: Ulcerative 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.

Methods: We 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.

Results: In 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.

Discussion: Notably, 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.

Keywords: bioinformatics analysis; colorectal cancer; cuproptosis; experimental verification; immune microenvironment; ulcerative colitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis*
Colitis, Ulcerative* / drug therapy
Computational Biology / methods
Copper / toxicity
Inflammatory Bowel Diseases* / complications
Mice

Substances

Copper

Grants and funding

This project was supported by grants from the National Key Research and Development Program (Grant No. 2019YFA0110703) to WW, the National Natural Science Foundation of China (No. 31800688), the Foundation of Liaoning Educational Committee of China (Grant No. LQN202011), and Shenyang Youth Science and Technology Innovation Project (No. RC220177) to ZY. The Science and Technology Innovation Foundation of Hunan Province (Grant No. 2020SK53614) awarded the grant to XM. The National Natural Science Foundation of China (Grant Nos. 82272102 and 81971721) awarded the grant to XM and WW.