Identification and validation of USP15 and CUL2 as ubiquitination related biomarker in chronic obstructive pulmonary disease

Abstract Purpose Ubiquitination is one of the important epigenetic modifications, influencing the development of various diseases. The objective of this study is to investigate the ubiquitination related genes in chronic obstructive pulmonary disease (COPD). Methods The gene microarray dataset from...

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Main Authors: Shulei Sun, Zhaoxiong Zhang, Haiyan Zhao
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Hereditas
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Online Access:https://doi.org/10.1186/s41065-025-00460-1
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author Shulei Sun
Zhaoxiong Zhang
Haiyan Zhao
author_facet Shulei Sun
Zhaoxiong Zhang
Haiyan Zhao
author_sort Shulei Sun
collection DOAJ
description Abstract Purpose Ubiquitination is one of the important epigenetic modifications, influencing the development of various diseases. The objective of this study is to investigate the ubiquitination related genes in chronic obstructive pulmonary disease (COPD). Methods The gene microarray dataset from COPD patients and ubiquitination related genes were analyzed. Venn diagram analysis was used to intersect differentially expressed genes and ubiquitination related genes. The functional enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were performed on differentially expressed ubiquitination related genes. Finally, we confirmed the expression of hub genes through qPCR and western blot experiments in clinical COPD patients and cell lines. Results We identified 2,932 differentially expressed genes and 96 differentially expressed ubiquitination related genes. GO analysis indicated that the differentially expressed ubiquitination related genes were mainly enriched in post-translational protein modification and ubiquitin ligase complex. KEGG analysis showed that ubiquitination related genes were mainly involved in ubiquitin mediated proteolysis and TNF signaling pathway. GSEA analysis suggested that some hub genes are involved in allograft rejection, IL6/JAK/STAT3 signaling and inflammatory response. Our qPCR and western blot experimental results indicate that the expression of USP15 and CUL2 is higher in COPD group compared to the control group, consistent with the bioinformatics analysis. Conclusion Our bioinformatics analysis and experimental results suggest that USP15 and CUL2 may contribute to the progression of COPD through ubiquitination modification. To our knowledge, this is the first study to demonstrate the involvement of USP15 and CUL2 in COPD. Our results may provide new insights into the diagnosis and treatment of COPD.
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spelling doaj-art-27f7b29135064d0bacf44cbc448709bc2025-08-20T03:08:25ZengBMCHereditas1601-52232025-05-01162111210.1186/s41065-025-00460-1Identification and validation of USP15 and CUL2 as ubiquitination related biomarker in chronic obstructive pulmonary diseaseShulei Sun0Zhaoxiong Zhang1Haiyan Zhao2Department of Respiratory and Critical Care Medicine, Tianjin Medical University General HospitalTianjin Medical University General HospitalDepartment of Respiratory and Critical Care Medicine, Tianjin Medical University General HospitalAbstract Purpose Ubiquitination is one of the important epigenetic modifications, influencing the development of various diseases. The objective of this study is to investigate the ubiquitination related genes in chronic obstructive pulmonary disease (COPD). Methods The gene microarray dataset from COPD patients and ubiquitination related genes were analyzed. Venn diagram analysis was used to intersect differentially expressed genes and ubiquitination related genes. The functional enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were performed on differentially expressed ubiquitination related genes. Finally, we confirmed the expression of hub genes through qPCR and western blot experiments in clinical COPD patients and cell lines. Results We identified 2,932 differentially expressed genes and 96 differentially expressed ubiquitination related genes. GO analysis indicated that the differentially expressed ubiquitination related genes were mainly enriched in post-translational protein modification and ubiquitin ligase complex. KEGG analysis showed that ubiquitination related genes were mainly involved in ubiquitin mediated proteolysis and TNF signaling pathway. GSEA analysis suggested that some hub genes are involved in allograft rejection, IL6/JAK/STAT3 signaling and inflammatory response. Our qPCR and western blot experimental results indicate that the expression of USP15 and CUL2 is higher in COPD group compared to the control group, consistent with the bioinformatics analysis. Conclusion Our bioinformatics analysis and experimental results suggest that USP15 and CUL2 may contribute to the progression of COPD through ubiquitination modification. To our knowledge, this is the first study to demonstrate the involvement of USP15 and CUL2 in COPD. Our results may provide new insights into the diagnosis and treatment of COPD.https://doi.org/10.1186/s41065-025-00460-1Ubiquitination related genesCOPDBioinformatics analysisUSP15CUL2
spellingShingle Shulei Sun
Zhaoxiong Zhang
Haiyan Zhao
Identification and validation of USP15 and CUL2 as ubiquitination related biomarker in chronic obstructive pulmonary disease
Hereditas
Ubiquitination related genes
COPD
Bioinformatics analysis
USP15
CUL2
title Identification and validation of USP15 and CUL2 as ubiquitination related biomarker in chronic obstructive pulmonary disease
title_full Identification and validation of USP15 and CUL2 as ubiquitination related biomarker in chronic obstructive pulmonary disease
title_fullStr Identification and validation of USP15 and CUL2 as ubiquitination related biomarker in chronic obstructive pulmonary disease
title_full_unstemmed Identification and validation of USP15 and CUL2 as ubiquitination related biomarker in chronic obstructive pulmonary disease
title_short Identification and validation of USP15 and CUL2 as ubiquitination related biomarker in chronic obstructive pulmonary disease
title_sort identification and validation of usp15 and cul2 as ubiquitination related biomarker in chronic obstructive pulmonary disease
topic Ubiquitination related genes
COPD
Bioinformatics analysis
USP15
CUL2
url https://doi.org/10.1186/s41065-025-00460-1
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AT zhaoxiongzhang identificationandvalidationofusp15andcul2asubiquitinationrelatedbiomarkerinchronicobstructivepulmonarydisease
AT haiyanzhao identificationandvalidationofusp15andcul2asubiquitinationrelatedbiomarkerinchronicobstructivepulmonarydisease