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

Abstract

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.

PANoptosis and Autophagy-Related Molecular Signature and Immune Landscape in Ulcerative Colitis: Integrated Analysis and Experimental Validation

“…While apoptosis, pyroptosis, necroptosis, and autophagy have been extensively investigated in UC, [47][48][49] recent research has also explored the involvement of ferroptosis and cuproptosis in this condition. 50,51 However, there is limited research on the regulatory 52 Through bioinformatics and experimental verification, our study identified key genes related to PANoptosis and autophagy, potentially influencing immune dysregulation and wound healing in UC.…”

Identification and validation of PANoptosis and autophagy-related molecular characterization in ulcerative colitis

“…and Disul dptosis [43]. The roles of apoptosis, pyroptosis, necroptosis, and autophagy have been extensively investigated in UC [44][45][46], and recently there has been a growing body of research exploring the involvement of ferroptosis and cuproptosis in UC [47,48]. However, there are no bioinformatics-based studies or experimental researches to demonstrate the regulatory role of PANoptosis in UC.…”

Comprehensive analysis of disulfidptosis-related genes reveals the effect of disulfidptosis in ulcerative colitis

“…Previous studies have revealed notable changes for the levels of various classical programmed cell death pathways in UC intestinal epithelial cells (IECs) and intestinal mucosal immune cells, such as apoptosis, necrosis, and pyroptosis, which in turn lead to an imbalance of the intestinal mucosal barrier and immune homeostasis in patients with UC, and are an important influence on the development of UC (Supplementary Table S1 - S3 ) 2 , 3 . Ferroptosis and cuproptosis have been successively discovered as novel modes of programmed cell death in recent years 4 , 5 , and their roles and mechanisms in UC are being successively reported, further revealing the key regulatory roles of novel modes of programmed cell death in UC intestinal mucosal homeostasis 6 – 8 . Therefore, further exploration of the changes and regulatory mechanisms of various types of programmed cell death in UC intestinal mucosal tissues will be beneficial for further elucidating the pathogenesis of UC and finding new therapeutic targets.…”