Long Noncoding Transcriptome in Chronic Obstructive Pulmonary Disease

Devadoss, Dinesh; Long, Christopher J.; Langley, Raymond J.; Manevski, Marko; Nair, M. G.; Campos, Michael; Borchert, Glen M.; Rahman, Irfan; Chand, Hitendra S.

doi:10.1165/rcmb.2019-0184tr

Cited by 43 publications

(45 citation statements)

References 83 publications

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“…LncRNAs play important roles in various biological processes and are emerging as reliable biomarkers and potential therapeutic targets of human chronic diseases [53,54]. However, comparatively few studies have reported the involvement of lncRNAs in chronic nasal in ammation.…”

Section: Discussionmentioning

confidence: 99%

Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

Wang

Luan

et al. 2020

Preprint

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Abstract Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the molecular endotypes associated with CRSwNP with comorbid asthma (CRSwNP+AS) are not clear. This study aimed to investigate the characteristics of type 2 inflammation and the molecular signatures associated with CRSwNP+AS. Methods: A total of 195 subjects; including 65 CRSwNP+AS patients, 99 patients with CRSwNP-alone, and 31 healthy control subjects; were enrolled in the study. Nasal tissues from patients with CRSwNP+AS, CRSwNP-alone and control subjects were assessed for infiltration of inflammatory cells and concentrations of total IgE. Whole-transcriptome sequencing was performed and differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated. Results: Significantly higher local eosinophil infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP+AS patients than in nasal tissues from CRSwNP-alone patients. Furthermore, atopy and recurrence were significantly more frequent in patients with CRSwNP+AS than in patients with CRSwNP-alone (62.5% vs 28.6% and 66.7% vs 26.9%, respectively). RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP+AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. Overall, 968 DE-mRNAs and 312 DE-lncRNAs were identified between CRSwNP+AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP+AS were mainly associated with higher activities of arachidonic acid metabolism, type 2 cytokines related pathway and fibrinolysis pathway, and lower activity of IL-17 signalling pathway. Furthermore, the expression of type 2 cytokines; IL5 and IL13, was positively correlated with local eosinophil infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP+AS. Conclusions: Patients with CRSwNP+AS have distinct type 2-high inflammation-associated molecular signatures in nasal tissues compared to patients with CRSwNP-alone.

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Section: Discussionmentioning

confidence: 99%

Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

Wang

Luan

et al. 2020

Preprint

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“…In this respect, evidences of involvement of exosomal lncRNA in lung pathologies including lung cancer, tuberculosis (TB), chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung disease (ILD) are increasing [1,[11][12][13][14][15]. It has been demonstrated that the exosomal microRNAs (miRNA) and lncRNA profiles among patients with pulmonary pathologies are quite distinct than healthy individuals [12,14,16,17].…”

Section: Introductionmentioning

confidence: 99%

Differential plasma exosomal long non-coding RNAs expression profiles and their emerging role in E-cigarette users, cigarette, waterpipe, and dual smokers

et al. 2020

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Long non-coding RNAs (lncRNAs) are the varied set of transcripts that play a critical role in biological processes like gene regulation, transcription, post-transcriptional modification, and chromatin remodeling. Recent studies have reported the presence of lncRNAs in the exosomes that are involved in regulating cell-to-cell communication in lung pathologies including lung cancer, chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). In this study, we compared the lncRNA profiles in the plasma-derived exosomes amongst non-smokers (NS), cigarette smokers (CS), E-cig users (E-cig), waterpipe smokers (WP) and dual smokers (CSWP) using GeneChip™ WT Pico kit for transcriptional profiling. We found alterations in a distinct set of lncRNAs among subjects exposed to E-cig vapor, cigarette smoke, waterpipe smoke and dual smoke with some overlaps. Gene enrichment analyses of the differentially expressed lncRNAs demonstrated enrichment in the lncRNAs involved in crucial biological processes including steroid metabolism, cell differentiation and proliferation. Thus, the characterized lncRNA profiles of the plasma-derived exosomes from smokers, vapers, waterpipe users, and dual smokers will help identify the biomarkers relevant to chronic lung diseases such as COPD, asthma or IPF.

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“…LncRNAs play important roles in various biological processes and are emerging as biomarkers and potential therapeutic targets of human chronic diseases [39][40]. However, very few studies have reported the involvement of lncRNAs in chronic nasal inflammation.…”

Section: Discussionmentioning

confidence: 99%

Distinct Type 2-high Inflammation Associated Molecular Phenotypes of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

Wang

Luan

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the phenotypes especially the molecular phenotypes of CRSwNP with comorbid asthma (CRSwNP+AS) are not clear. This study aimed to investigate the molecular phenotypes associated with CRSwNP+AS. Methods Nasal tissues from patients with CRSwNP+AS, CRSwNP-alone and control subjects were assessed with infiltrated inflammatory cells and concentrations of total IgE, and performed whole-transcriptome sequencing. Differentially expressed mRNAs (DE-mRNAs) and lncRNAs (DE-lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated. Results More local eosinophils infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP+AS than from CRSwNP-alone. RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP+AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. We identified 968 DE-mRNAs and 312 DE-lncRNAs between CRSwNP+AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP+AS were mainly associated with higher activities of arachidonic acid metabolism, Th2 cytokines related pathway and fibrinolysis pathway, and oppositely lower activities of IL-17 signaling pathway. We further showed that the expression of Th2 cytokines, IL5 and IL13, were positively correlated with local eosinophils infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP+AS. Conclusions Patients with CRSwNP+AS have distinct type 2-high inflammation and its associated transcriptome signatures in nasal tissues compared to patients with CRSwNP alone.

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Long Noncoding Transcriptome in Chronic Obstructive Pulmonary Disease

Cited by 43 publications

References 83 publications

Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

Differential plasma exosomal long non-coding RNAs expression profiles and their emerging role in E-cigarette users, cigarette, waterpipe, and dual smokers

Distinct Type 2-high Inflammation Associated Molecular Phenotypes of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

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