Identification and validation of CDC20 and ITCH as ubiquitination related biomarker in idiopathic pulmonary fibrosis.

IF 2.5 3区生物学 Hereditas Pub Date : 2025-04-01 DOI:10.1186/s41065-025-00401-y

Shulei Sun, Yubao Wang, Jing Feng

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Abstract

Purpose: Ubiquitination plays a crucial role in various diseases. This study aims to explore the potential ubiquitination related genes in IPF.

Methods: The gene microarray dataset GSE24206 was obtained from GEO database. Subsequently, through differential expression analysis and molecular signatures database, we obtained 1734 differentially expressed genes and 742 ubiquitination related genes. Through the venn diagram analysis, we obtained 53 differentially expressed ubiquitination related genes. Then, gene-ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interactions (PPI) and gene set enrichment analysis (GSEA) were applied for the differentially expressed ubiquitination related genes. Finally, the expression of CDC20 and ITCH in IPF patients and cells were validated by qPCR and western blot assay.

Results: A total of 53 differentially expressed ubiquitination related genes (36 up-regulated genes and 17 down-regulated genes) were identified between 17 IPF patients and 6 healthy controls. GO and KEGG enrichment analysis of ubiquitination related genes mainly involved in regulation of protein ubiquitination, regulation of post-translational protein modification and ubiquitin mediated proteolysis. The PPI results demonstrated that these ubiquitination related genes interacted with each other. The GSEA analysis results for some of the hub genes mainly involved epithelial mesenchymal transition, inflammatory response, hypoxia, and apoptosis. The experiment expression level of CDC20 and ITCH in IPF patients and IPF cells were consistent with the bioinformatics analysis results.

Conclusion: We identified 53 potential ubiquitination related genes of IPF through bioinformatics analysis. CDC20 and ITCH and other ubiquitination related genes may influence the development of IPF through epithelial mesenchymal transition and inflammatory response. Our research findings provide insights into the mechanisms of fibrosis and may provide evidence for potential therapeutic targets for fibrosis.

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CDC20和ITCH作为特发性肺纤维化泛素化相关生物标志物的鉴定和验证。

目的：泛素化在多种疾病中起重要作用。本研究旨在探索IPF中潜在的泛素化相关基因。方法：从GEO数据库中获取基因微阵列数据集GSE24206。随后，通过差异表达分析和分子特征数据库，我们获得了1734个差异表达基因和742个泛素化相关基因。通过维恩图分析，我们得到53个差异表达的泛素化相关基因。然后，对差异表达的泛素化相关基因进行基因本体（GO）富集分析、京都基因与基因组百科全书（KEGG）途径富集分析、蛋白-蛋白相互作用（PPI）和基因集富集分析（GSEA）。最后，通过qPCR和western blot验证IPF患者和细胞中CDC20和ITCH的表达。结果：17例IPF患者与6例健康对照者共鉴定出53个差异表达的泛素化相关基因（36个上调基因，17个下调基因）。泛素化相关基因的GO和KEGG富集分析主要涉及蛋白泛素化调控、翻译后蛋白修饰调控和泛素介导的蛋白水解。PPI结果表明，这些泛素化相关基因相互作用。部分枢纽基因的GSEA分析结果主要涉及上皮间质转化、炎症反应、缺氧和细胞凋亡。CDC20和ITCH在IPF患者和IPF细胞中的实验表达水平与生物信息学分析结果一致。结论：通过生物信息学分析，鉴定出53个IPF泛素化相关基因。CDC20和ITCH等泛素化相关基因可能通过上皮间质转化和炎症反应影响IPF的发展。我们的研究结果提供了对纤维化机制的见解，并可能为纤维化的潜在治疗靶点提供证据。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.