Integrative analysis of ferroptosis-related genes in ulcerative colitis.

Integrative analysis of ferroptosis-related genes in ulcerative colitis.
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DOI:
10.1177/03000605211042975
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发表时间:
2021-09
期刊:
The Journal of international medical research
影响因子:
--
通讯作者:
Han L
Han L
中科院分区:
其他
文献类型:
--
作者:
Cui DJ;Chen C;Yuan WQ;Yang YH;Han L

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本研究的目的是鉴定和验证溃疡性结肠炎(UC)的铁中毒相关标志物,以探索UC诊断和治疗的新方向。我们从基因表达综合数据库(GEO)、FerDb和GeneCards数据库中筛选了UC芯片和铁中毒相关基因。应用生物信息学方法分析UC组与正常对照组的差异表达基因(DEG)及亚铁代谢相关基因。富集分析,蛋白质-蛋白质相互作用分析,和枢纽基因进行了筛选。采用外周血芯片和动物实验对铁中毒相关hub基因进行验证。最后,构建了hub基因-转录因子、hub基因-microRNA(miRNA)和hub基因-药物相互作用网络。总体而言,26个铁中毒相关的DEG被确定为在能量途径和代谢中显著富集。我们从蛋白质-蛋白质相互作用网络中鉴定了10个与铁中毒相关的中枢基因:IL 6、PTGS 2、HIF 1A、CD 44、MUC 1、CAV 1、NOS 2、CXCL 2、SCD和ACSL 4。在外周血芯片GSE 94648中,CD 44和MUC 1上调,这与GSE 75214中的表达趋势一致。动物实验表明,结肠中CD 44表达显著增加。我们的研究结果表明,CD 44和MUC 1可能是UC中的铁凋亡相关标志物。
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. 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. 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: IL6, PTGS2, HIF1A, CD44, MUC1, CAV1, NOS2, CXCL2, SCD, and ACSL4. In the peripheral blood chip GSE94648, CD44 and MUC1 were upregulated, which was consistent with the expression trend in GSE75214. Animal experiments showed that CD44 expression was significantly increased in the colon. Our findings indicate that CD44 and MUC1 may be ferroptosis-related markers in UC.
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