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As a procedural death path that integrates the above-mentioned many deaths, the role of PANoptosis in UC has not been clarified. This study aims to explore the characterization of PANoptosis patterns and determine the potential biomarkers and therapeutic targets. We constructed a PANoptosis gene set and revealed significant activation of PANoptosis in UC patients based on multiple transcriptome profiles of intestinal mucosal biopsies from the GEO database. Comprehensive bioinformatics analysis revealed five key genes (ZBP1, AIM2, CASP1\/8, IRF1) of PANoptosome with good diagnostic value and were highly correlated with an increase in pro-inflammatory immune cells and factors. In addition, we established a reliable ceRNA regulatory network of PANoptosis and predicted three potential small-molecule drugs sharing calcium channel blockers that were identified, among which flunarizine exhibited the highest correlation with a high binding affinity to the targets. Finally, we used the DSS-induced colitis model to validate our findings. This study identifies key genes of PANoptosis associated with UC development and hypothesizes that IRF1 as a TF promotes PANoptosome multicomponent expression, activates PANoptosis, and then induces IECs excessive death.<\/jats:p>","DOI":"10.3390\/ijms25010348","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T02:58:12Z","timestamp":1703645892000},"page":"348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Comprehensive Analysis of PANoptosis-Related Gene Signature of Ulcerative Colitis"],"prefix":"10.3390","volume":"25","author":[{"given":"Jun-Meng","family":"Wang","sequence":"first","affiliation":[{"name":"Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Yu","family":"Xia","sequence":"additional","affiliation":[{"name":"Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Mei","family":"Wang","sequence":"additional","affiliation":[{"name":"Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Bing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Huang","sequence":"additional","affiliation":[{"name":"Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Feng","sequence":"additional","affiliation":[{"name":"Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Shuang","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Guang","family":"Yu","sequence":"additional","affiliation":[{"name":"Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao-Feng","family":"Wu","sequence":"additional","affiliation":[{"name":"Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Acupuncture & Chronobiology Key Laboratory of Sichuan Province, Chengdu 611137, China"},{"name":"Key Laboratory of Acupuncture for Senile Disease, Chengdu University of TCM, Ministry of Education, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41575-020-0326-4","article-title":"Cell death in the gut epithelium and implications for chronic inflammation","volume":"17","author":"Patankar","year":"2020","journal-title":"Nat. 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