Integrative Analysis of Ferroptosis-related Genes in Ulcerative Colitis

Overview

Journal J Int Med Res

Publisher Sage Publications

Specialty General Medicine

Date 2021 Sep 13

PMID 34510961

Citations 18

Authors

De-Jun Cui

Chen Chen

Wen-Qiang Yuan

Yun-Han Yang

Lu Han

Affiliations

Soon will be listed here.

Abstract

Objective: The aim of this study was to identify and validate ferroptosis-related markers in ulcerative colitis (UC) to explore new directions for UC diagnosis and treatment.

Methods: We screened UC chips and ferroptosis-related genes from the Gene Expression Omnibus (GEO), FerrDb, and GeneCards databases. The differentially expressed genes (DEGs) and ferroptosis-related DEGs between the UC group and normal controls were analyzed using bioinformatics methods. Enrichment analysis, protein-protein interaction analysis, and hub genes were screened. Peripheral blood chip and animal experiments were used to validate the ferroptosis-related hub genes. Finally, hub gene-transcription factor, hub gene-microRNA (miRNA), and hub gene-drug interaction networks were constructed.

Results: Overall, 26 ferroptosis-related DEGs were identified that were significantly enriched in energy pathways and metabolism. We identified ten ferroptosis-related hub genes from the protein-protein interaction network: , , , , , , , , , and . In the peripheral blood chip GSE94648, and were upregulated, which was consistent with the expression trend in GSE75214. Animal experiments showed that expression was significantly increased in the colon.

Conclusions: Our findings indicate that and may be ferroptosis-related markers in UC.

Citing Articles

Machine learning-based bulk RNA analysis reveals a prognostic signature of 13 cell death patterns and potential therapeutic target of SMAD3 in acute myeloid leukemia.

Bao X, Chen Y, Chang J, Du J, Yang C, Wu Y BMC Cancer. 2025; 25(1):273.

PMID: 39955536 PMC: 11830216. DOI: 10.1186/s12885-025-13658-3.

Co-delivery of siRNA and cisplatin via electrospun Nanofibrous membranes for synergistic treatment of malignant melanoma.

Zhang X, Zheng G, Zhou Z, Zhu M, Tang S Heliyon. 2024; 10(17):e37517.

PMID: 39290263 PMC: 11407083. DOI: 10.1016/j.heliyon.2024.e37517.

Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway.

Lan J, Deng Z, Wang Q, Li D, Fan K, Chang J Int J Biol Sci. 2024; 20(7):2507-2531.

PMID: 38725846 PMC: 11077368. DOI: 10.7150/ijbs.94548.

Identification of marker genes associated with N6-methyladenosine and autophagy in ulcerative colitis.

Liu X, Qiao D, Zhang Y, Liu Z, Chen Y, Que R World J Clin Cases. 2024; 12(10):1750-1765.

PMID: 38660076 PMC: 11036473. DOI: 10.12998/wjcc.v12.i10.1750.

Deciphering Ferroptosis: From Molecular Pathways to Machine Learning-Guided Therapeutic Innovation.

Mete M, Ojha A, Dhar P, Das D Mol Biotechnol. 2024; .

PMID: 38613722 DOI: 10.1007/s12033-024-01139-0.

References

Feuerstein J, Isaacs K, Schneider Y, Siddique S, Falck-Ytter Y, Singh S . AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis. Gastroenterology. 2020; 158(5):1450-1461. PMC: 7175923. DOI: 10.1053/j.gastro.2020.01.006. View

Chin C, Chen S, Wu H, Ho C, Ko M, Lin C . cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014; 8 Suppl 4:S11. PMC: 4290687. DOI: 10.1186/1752-0509-8-S4-S11. View

Chen E, Tan C, Kou Y, Duan Q, Wang Z, Meirelles G . Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013; 14:128. PMC: 3637064. DOI: 10.1186/1471-2105-14-128. View

Mehandru S, Colombel J . The intestinal barrier, an arbitrator turned provocateur in IBD. Nat Rev Gastroenterol Hepatol. 2020; 18(2):83-84. DOI: 10.1038/s41575-020-00399-w. View

Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View

Rubin D, Ananthakrishnan A, Siegel C, Sauer B, Long M . ACG Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol. 2019; 114(3):384-413. DOI: 10.14309/ajg.0000000000000152. View

Cui D, Yang X, Okuda S, Ling Y, Zhang Z, Liu Q . Gallincin ameliorates colitis-associated inflammation and barrier function in mice based on network pharmacology prediction. J Int Med Res. 2020; 48(12):300060520951023. PMC: 7745594. DOI: 10.1177/0300060520951023. View

Kobayashi Y, Ohfuji S, Kondo K, Fukushima W, Sasaki S, Kamata N . Association between dietary iron and zinc intake and development of ulcerative colitis: A case-control study in Japan. J Gastroenterol Hepatol. 2019; 34(10):1703-1710. DOI: 10.1111/jgh.14642. View

Kobayashi T, Siegmund B, Le Berre C, Wei S, Ferrante M, Shen B . Ulcerative colitis. Nat Rev Dis Primers. 2020; 6(1):74. DOI: 10.1038/s41572-020-0205-x. View

10.

Kuleshov M, Jones M, Rouillard A, Fernandez N, Duan Q, Wang Z . Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016; 44(W1):W90-7. PMC: 4987924. DOI: 10.1093/nar/gkw377. View

11.

Wang S, Liu W, Wang J, Bai X . Curculigoside inhibits ferroptosis in ulcerative colitis through the induction of GPX4. Life Sci. 2020; 259:118356. DOI: 10.1016/j.lfs.2020.118356. View

12.

Carrier J, Aghdassi E, Jeejeebhoy K, Allard J . Exacerbation of dextran sulfate sodium-induced colitis by dietary iron supplementation: role of NF-kappaB. Int J Colorectal Dis. 2005; 21(4):381-7. DOI: 10.1007/s00384-005-0011-7. View

13.

Conrad M, Lorenz S, Proneth B . Targeting Ferroptosis: New Hope for As-Yet-Incurable Diseases. Trends Mol Med. 2020; 27(2):113-122. DOI: 10.1016/j.molmed.2020.08.010. View

14.

Xu M, Tao J, Yang Y, Tan S, Liu H, Jiang J . Ferroptosis involves in intestinal epithelial cell death in ulcerative colitis. Cell Death Dis. 2020; 11(2):86. PMC: 6997394. DOI: 10.1038/s41419-020-2299-1. View

15.

Sun Y, Fan L, Mian W, Zhang F, Liu X, Tang Y . Modified apple polysaccharide influences MUC-1 expression to prevent ICR mice from colitis-associated carcinogenesis. Int J Biol Macromol. 2018; 120(Pt B):1387-1395. DOI: 10.1016/j.ijbiomac.2018.09.142. View

16.

Xu S, He Y, Lin L, Chen P, Chen M, Zhang S . The emerging role of ferroptosis in intestinal disease. Cell Death Dis. 2021; 12(4):289. PMC: 7969743. DOI: 10.1038/s41419-021-03559-1. View

17.

Zhou N, Bao J . FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database (Oxford). 2020; 2020. PMC: 7100629. DOI: 10.1093/database/baaa021. View

18.

Chen Y, Zhang P, Chen W, Chen G . Ferroptosis mediated DSS-induced ulcerative colitis associated with Nrf2/HO-1 signaling pathway. Immunol Lett. 2020; 225:9-15. DOI: 10.1016/j.imlet.2020.06.005. View

19.

Millar A, Rampton D, Blake D . Effects of iron and iron chelation in vitro on mucosal oxidant activity in ulcerative colitis. Aliment Pharmacol Ther. 2000; 14(9):1163-8. DOI: 10.1046/j.1365-2036.2000.00828.x. View

20.

Vancamelbeke M, Vanuytsel T, Farre R, Verstockt S, Ferrante M, Van Assche G . Genetic and Transcriptomic Bases of Intestinal Epithelial Barrier Dysfunction in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2017; 23(10):1718-1729. PMC: 6461205. DOI: 10.1097/MIB.0000000000001246. View