Identification of Hub Genes Associated with COPD Through Integrated Bioinformatics Analysis

Chen, Lin; Zhu, Donglan; Huang, Jinfu; Zhang, Hui; Guang, Zhou; Zhong, Xiaoning

doi:10.2147/copd.s353765

Cited by 11 publications

(6 citation statements)

References 53 publications

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“…With the evolution of the high-throughput sequencing technology and bioinformatics analysis, the ceRNA network hypothesis may illustrates the occurrence and progression of disease partially. Despite an increasing number of studies on ceRNA networks, it was not been fully elaborated about the molecular mechanisms of COPD ( Salmena et al, 2011 ; Gong et al, 2020 ; Chen et al, 2022 ). In the present study, we utilized the whole transcriptome sequencing analysis of two groups (seven patients with COPD and six non-COPD control subjects), screened out 1,796 DEmRNAs (796 upregulated and 1,000 downregulated), 2,207 DElncRNAs (1,245 upregulated and 963 downregulated), and 11 DEmiRNA (five upregulated and six downregulated).…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis of the expression profiles of whole coding and non-coding RNA transcriptomes and construction of the competing endogenous RNA networks for chronic obstructive pulmonary disease

Feng

Dong

et al. 2023

Front. Genet.

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The pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) is implicated in airway inflammation, oxidative stress, protease/anti-protease and emphysema. Abnormally expressed non-coding RNAs (ncRNAs) play a vital role in regulation of COPD occurrence and progression. The regulatory mechanisms of the circRNA/lncRNA-miRNA-mRNA (competing endogenous RNA, ceRNA) networks might facilitate our cognition of RNA interactions in COPD. This study aimed to identified novel RNA transcripts and constructed the potential ceRNA networks of COPD patients. Total transcriptome sequencing of the tissues from patients with COPD (COPD) (n = 7) and non-COPD control subjects (Normal) (n = 6) was performed, and the expression profiles of differentially expressed genes (DEGs), including mRNAs, lncRNAs, circRNAs, and miRNAs, were analyzed. The ceRNA network was established based on the miRcode and miRanda databases. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and Gene set variation analysis (GSVA) were implemented for functional enrichment analysis of DEGs. Finally, CIBERSORTx was extracted to analyze the relevance between hub genes and various immune cells.The Starbase and JASPAR databases were used to construct hub-RNA binding proteins (RBPs) and lncRNA-transcription factor (TF) interaction networks. A total of 1,796 mRNAs, 2,207 lncRNAs, and 11 miRNAs showed differentially expression between the lung tissue samples from the normal and COPD groups. Based on these DEGs, lncRNA/circRNA-miRNA-mRNA ceRNA networks were constructed respectively. In addition, ten hub genes were identified. Among them, RPS11, RPL32, RPL5, and RPL27A were associated with the proliferation, differentiation, and apoptosis of the lung tissue. The biological function revealed that TNF–α via NF–kB and IL6/JAK/STAT3 signaling pathways were involved in COPD. Our research constructed the lncRNA/circRNA-miRNA-mRNA ceRNA networks, filtrated ten hub genes may regulate the TNF-α/NF-κB, IL6/JAK/STAT3 signally pathways, which indirectly elucidated the post-transcriptional regulation mechanism of COPD and lay the foundation for excavating the novel targets of diagnosis and treatment in COPD.

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Section: Discussionmentioning

confidence: 99%

Integrative analysis of the expression profiles of whole coding and non-coding RNA transcriptomes and construction of the competing endogenous RNA networks for chronic obstructive pulmonary disease

Feng

Dong

et al. 2023

Front. Genet.

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“…Since COPD exome and transcriptome sequencing often incriminated cilia-associated genes [ 1 , 3 , 14 , 15 ], the identification, the molecular characterization and the clinical validation of these key actors appeared to be highly significant in respiratory research. Additionally, we unveiled the genetic alterations of two hits that were previously suggested as a useful biomarker of smokers at risk of developing COPD (COL14A1, [ 16 ]) and emphysema-associated regulator (AMOTL1, [ 17 ]). Delving deeper into the characterization of variants and CNA in lung cancer may provide additional molecular insights into the relationship between COPD and lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Whole-Exome Sequencing of Bronchial Epithelial Cells Reveals a Genetic Print of Airway Remodelling in COPD

et al. 2022

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The remodelling of the airways is a hallmark of chronic obstructive pulmonary disease, but it is highly heterogeneous and erratically distributed in the airways. To assess the genetic print of remodelling in chronic obstructive pulmonary disease (COPD), we performed a comparative whole-exome sequencing analysis on microdissected bronchial epithelia. Lung resections from four non-COPD and three COPD subjects (ex-smokers and current smokers) were formalin-fixed paraffin-embedded (FFPE). Non-remodelled and remodelled bronchial epithelia were isolated by laser microdissection. Genomic DNA was captured and sequenced. The comparative quantitative analysis identified a list of 109 genes as having variants in remodelled epithelia and 160 genes as having copy number alterations in remodelled epithelia, mainly in COPD patients. The functional analysis highlighted cilia-associated processes. Therefore, bronchial-remodelled epithelia appeared genetically more altered than non-remodelled epithelia. Characterizing the unique molecular print of airway remodelling in respiratory diseases may help uncover additional factors contributing to epithelial dysfunctions, ultimately providing additional targetable proteins to correct epithelial remodelling and improve lung function.

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“…2017-KY-NSFC-111) and it was in line with the Laboratory Animal—Guideline for ethical review of animal welfare (GB/T 35892-2018). The mean linear intercept (Lm) was used to assess emphysemaseverity in mice 33 . Sections of three different areas (excluding the atmospheric tract and blood vessels) of each mouse were selected and read by two pathologists in a blinded manner.…”

Section: Methodsmentioning

confidence: 99%

Identification of related-genes of T cells in lung tissue of chronic obstructive pulmonary disease based on bioinformatics and experimental validation

Xue,

Dong,

Gao

et al. 2024

Sci Rep

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T cells are one of the main cell types shaping the immune microenvironment in chronic obstructive pulmonary disease (COPD). They persist andplay cytotoxic roles. The purpose of this study aimed to explore the potential related-genes of T cells in lung tissue of COPD. Chip data GSE38974 and single_celldata GSE196638 were downloaded from the GEO database. Difference analyses and WGCNA of GSE38974 were performed to identify DEGs and the modules most associated with the COPD phenotype. Various cell subsets were obtained by GSE196638, and DEGs of T cells were further identified. GO, GSEA and KEGG enrichment analyses were conducted to explore the biological functions and regulatory signaling pathways of the DEGs and DEGs of T cells. The intersection of the DEGs, module genes and DEGs of T cells was assessed to acquire related-genes of T cells. The mRNA and protein expression levels of related-genes ofT cells were verified in lung tissue of mouse with emphysema model. Based on GSE38974 difference analysis, 3811 DEGs were obtained. The results of WGCNA showed that the red module had the highest correlation coefficient with the COPD phenotype. GSE196638 analysis identified 124 DEGs of T cells. The GO, GSEAand KEGG enrichment analyses mainly identified genes involved in I-kappaB kinase/NF-kappaB signaling, receptor signaling pathway via STAT, regulationof CD4-positive cells, regulation of T-helper cell differentiation, chemokine signaling pathway, Toll-likereceptor signaling pathway, CD8-positive cells, alpha–beta T cell differentiation, MAPK signaling pathway and Th17 cell differentiation. The DEGs, genes of the red module and DEGs of T cells were overlapped to acquire FOXO1 and DDX17. The results of RT-qPCR and Western Blot indicate that the mRNA and protein expression levels of FOXO1 and DDX17 in lung tissue of emphysema mice were significantly higher compared with those in air-exposed mice. FOXO1 as well as DDX17 may be related-genesof T cells in lung tissue of patient with COPD, and their participation in the biological processes of different signaling pathways may inspire further COPD research.

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Identification of Hub Genes Associated with COPD Through Integrated Bioinformatics Analysis

Cited by 11 publications

References 53 publications

Integrative analysis of the expression profiles of whole coding and non-coding RNA transcriptomes and construction of the competing endogenous RNA networks for chronic obstructive pulmonary disease

Integrative analysis of the expression profiles of whole coding and non-coding RNA transcriptomes and construction of the competing endogenous RNA networks for chronic obstructive pulmonary disease

Whole-Exome Sequencing of Bronchial Epithelial Cells Reveals a Genetic Print of Airway Remodelling in COPD

Identification of related-genes of T cells in lung tissue of chronic obstructive pulmonary disease based on bioinformatics and experimental validation

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