scholarly journals microRNA–mRNA regulatory networks underlying chronic mucus hypersecretion in COPD

2018 ◽  
Vol 52 (3) ◽  
pp. 1701556 ◽  
Author(s):  
Hataitip Tasena ◽  
Alen Faiz ◽  
Wim Timens ◽  
Jacobien Noordhoek ◽  
Machteld N. Hylkema ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Target Genes ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Mucus Hypersecretion ◽  
Mrna Targets ◽  
Copd Patients

Chronic mucus hypersecretion (CMH) is a common feature in chronic obstructive pulmonary disease (COPD) and is associated with worse prognosis and quality of life. This study aimed to identify microRNA (miRNA)–mRNA regulatory networks underlying CMH.The expression profiles of miRNA and mRNA in bronchial biopsies from 63 COPD patients were associated with CMH using linear regression. Potential mRNA targets of each CMH-associated miRNA were identified using Pearson correlations. Gene set enrichment analysis (GSEA) and STRING (search tool for the retrieval of interacting genes/proteins) analysis were used to identify key genes and pathways.20 miRNAs and 539 mRNAs were differentially expressed with CMH in COPD. The expression of 10 miRNAs was significantly correlated with the expression of one or more mRNAs. Of these, miR-134-5p, miR-146a-5p and the let-7 family had the highest representation of CMH-associated mRNAs among their negatively correlated predicted targets. KRAS and EDN1 were identified as key regulators of CMH and were negatively correlated predicted targets of miR-134-5p and let-7a-5p, let-7d-5p, and let-7f-5p, respectively. GSEA suggested involvement of MUC5AC-related genes and several other relevant gene sets in CMH. The lower expression of miR-134-5p was confirmed in primary airway fibroblasts from COPD patients with CMH.We identified miR-134-5p, miR-146a-5p and let-7 family, along with their potential target genes including KRAS and EDN1, as potential key miRNA–mRNA networks regulating CMH in COPD.

scholarly journals GPNMB contributes to a vicious circle for chronic obstructive pulmonary disease

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xi-Juan Zhang ◽  
Zhong-Hua Cui ◽  
Yan Dong ◽  
Xiu-Wen Liang ◽  
Yan-Xin Zhao ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Large Scale ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Chronic Obstructive ◽  
P Value ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Size Population

Abstract Osteoporosis (OP) is significant and debilitating comorbidity of chronic obstructive pulmonary disease (COPD). We hypothesize that genetic variance identified with OP may also play roles in COPD. We have conducted a large-scale relation data analysis to explore the genes implicated with either OP or COPD, or both. Each gene linked to OP but not to COPD was further explored in a mega-analysis and partial mega-analysis of 15 independently collected COPD RNA expression datasets, followed by gene set enrichment analysis (GSEA) and literature-based pathway analysis to explore their functional linked to COPD. A multiple linear regression (MLR) model was built to study the possible influence of sample size, population region, and study date on the gene expression data in COPD. At the first step of the analysis, we have identified 918 genes associated with COPD, 581 with OP, and a significant overlap (P<2.30e-140; 210 overlapped genes). Partial mega-analysis showed that, one OP gene, GPNMB presented significantly increased expression in COPD patients (P-value = 0.0018; log fold change = 0.83). GPNMB was enriched in multiple COPD pathways and plays roles as a gene hub formulating multiple vicious COPD pathways included gene MMP9 and MYC. GPNMB could be a novel gene that plays roles in both COPD and OP. Partial mega-analysis is valuable in identify case-specific genes for COPD.

scholarly journals Identification of Inflammation-Related Biomarker Lp-PLA2 for Patients With COPD by Comprehensive Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingming Deng ◽  
Yan Yin ◽  
Qin Zhang ◽  
Xiaoming Zhou ◽  
Gang Hou
Keyword(s):  
Exercise Tolerance ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Go Enrichment ◽  
Potential Biomarker ◽  
Immune Pathway

PurposeChronic obstructive pulmonary disease (COPD) is a complex and persistent lung disease and lack of biomarkers. The aim of this study is to screen and verify effective biomarkers for medical practice.MethodsDifferential expressed genes analysis and weighted co-expression network analysis were used to explore potential biomarker. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA) analysis were used to explore potential mechanism. CIBERSORTx website was used to evaluate tissue-infiltrating immune cells. Enzyme-linked immunosorbent assay (ELISA) was used to assess the concentrations of the Lp-PLA2 in serum.ResultsTen genes were selected via combined DEGs and WGCNA. Furthermore, PLA2G7 was choose based on validation from independent datasets. Immune infiltrate and enrichment analysis suggest PLA2G7 may regulate immune pathway via macrophages. Next, Lp-PLA2(coded by PLA2G7 gene) level was upregulated in COPD patients, increased along with The Global Average of COPD (GOLD) stage. In additional, Lp-PLA2 level was significant correlate with FEV1/FVC, BMI, FFMI, CAT score, mMRC score and 6MWD of COPD patients. Finally, the predictive efficiency of Lp-PLA2 level (AUC:0.796) and derived nomogram model (AUC:0.884) in exercise tolerance was notably superior to that of the sit-to-stand test and traditional clinical features.ConclusionLp-PLA2 is a promising biomarker for COPD patients and is suitable for assessing exercise tolerance in clinical practice.

scholarly journals CUL1-Mediated Organelle Fission Pathway Inhibits the Development of Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ran Li ◽  
Feng Xu ◽  
Xiao Wu ◽  
Shaoping Ji ◽  
Ruixue Xia
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Transcription Factors ◽  
Pulmonary Disease ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Development Trend ◽  
Chronic Obstructive ◽  
Hypergeometric Test ◽  
Obstructive Pulmonary Disease ◽  
Depth Analysis

Chronic obstructive pulmonary disease (COPD) is a global high-incidence chronic airway inflammation disease. Its deterioration will lead to more serious lung lesions and even lung cancer. Therefore, it is urgent to determine the pathogenesis of COPD and find potential therapeutic targets. The purpose of this study is to reveal the molecular mechanism of COPD disease development through in-depth analysis of transcription factors and ncRNA-driven pathogenic modules of COPD. We obtained the expression profile of COPD-related microRNAs from the NCBI-GEO database and analyzed the differences among groups to identify the microRNAs significantly associated with COPD. Then, their target genes are predicted and mapped to a protein-protein interaction (PPI) network. Finally, key transcription factors and the ncRNA of the regulatory module were identified based on the hypergeometric test. The results showed that CUL1 was the most interactive gene in the highly interactive module, so it was recognized as a dysfunctional molecule of COPD. Enrichment analysis also showed that it was much involved in the biological process of organelle fission, the highest number of regulatory modules. In addition, ncRNAs, mainly composed of miR-590-3p, miR-495-3p, miR-186-5p, and transcription factors such as MYC, BRCA1, and CDX2, significantly regulate COPD dysfunction blocks. In summary, we revealed that the COPD-related target gene CUL1 plays a key role in the potential dysfunction of the disease. It promotes the proliferation of fibroblast cells in COPD patients by mediating functional signals of organelle fission and thus participates in the progress of the disease. Our research helps biologists to further understand the etiology and development trend of COPD.

scholarly journals CircRNA Expression Profile in Lung Cancer Complicated with Chronic Obstructive Pulmonary Disease Patients

2020 ◽  
Author(s):  
Fuqiang Wen ◽  
Xiaoou Li ◽  
Yongchun Shen ◽  
Jiahan Cheng ◽  
Jun Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Expression Profiles ◽  
Circular Rnas ◽  
Chronic Obstructive ◽  
Biological Processes ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Diagnosis Of Lung Cancer

Abstract Background: Lung cancer complicated with chronic obstructive pulmonary disease (COPD) are major causes of mortality worldwide, and the incidence of lung cancer and COPD increasing significantly. Circular RNAs (circRNAs), have been reported to participate in various biological processes, whereas the role of circRNAs in lung cancer complicated with COPD remains unclear. We aims to identify differentially expressed circRNAs (DEcircRNAs) between lung cancer complicated with COPD and lung cancer without COPD. Method: The circRNAs expression profiles were identified using a high-throughput circRNA microarray in cancer adjacent tissues from 6 lung cancer without COPD patients and 8 lung cancer complicated with COPD patients. Bioinformatic analyses were conducted to identify the functions of DEcircRNAs. Result: A total of 115 up- and 128 down-regulated circRNAs were screened in lung cancer complicated with COPD patients compared with lung cancer without COPD patients. The myD88-dependent toll-like receptor signaling pathway and positive regulation of nitric oxide biosynthetic process ranked the top 2 enriched biological processes in Gene Ontology analysis. Signaling transduction and infectious diseases were the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways in both up- and down-regulated circRNAs. Compared with lung cancer without COPD, circRNAs are dysregulated in the adjacent tissues of lung cancer with COPD. Conclusion: The DEcircRNAs might act as potential targets for the diagnosis of lung cancer with COPD.

scholarly journals Pla2g2a Attenuates Colon Tumorigenesis in Azoxymethane-Treated C57BL/6 Mice; Expression Studies Reveal Pla2g2a Target Genes and Pathways

2009 ◽  
Vol 31 (5) ◽  
pp. 345-356
Author(s):  
Remond J. A. Fijneman ◽  
Lindsey K. Bade ◽  
Johannes R. Peham ◽  
Mark A. van de Wiel ◽  
Victor W. M. van Hinsbergh ◽  
...  
Keyword(s):  
Target Genes ◽  
Expression Profiles ◽  
Wnt Signaling Pathway ◽  
Enrichment Analysis ◽  
Germline Mutations ◽  
Gene Set Enrichment Analysis ◽  
Colon Tumorigenesis ◽  
Expression Studies ◽  
Microbial Defense ◽  
Microarray Expression

Background: The group IIA secretory phospholipase A2 gene, Pla2g2a, confers resistance to intestinal tumorigenesis in the ApcMin/+ mouse model. However, it is unclear how Pla2g2a exerts its tumor-suppressive effects and whether its mode of action depends on Apc-germline mutations.Methods: We tested whether expression of a Pla2g2a transgene provides protection against carcinogen-induced colon tumors, and examined whether the normal colon microenvironment is modulated by Pla2g2a expression.Results: Pla2g2a strongly inhibited colon tumorigenesis in mice following treatment with the DNA alkylating agent azoxymethane (AOM). Moreover, AOM-induced duodenal tumors were also attenuated by Pla2g2a expression. These tumors demonstrated upregulation of β-catenin, indicative of involvement of the Wnt signaling pathway. Comparison of genome-wide microarray expression profiles of healthy (non-pathologic) colon tissues from Pla2g2a-transgenic to non-transgenic mice revealed 382 genes that were differentially expressed, comprising clusters of genes involved in inflammation and microbial defense, cell signaling and cell cycle, transactivation, apoptosis and mitochondrial function, DNA repair, and lipid and energy metabolism. Pathway analysis using Gene Set Enrichment Analysis (GSEA) indicated that Pla2g2a suppresses the expression of interferon-induced genes.Conclusion: Our results demonstrate that Pla2g2a attenuates colon tumorigenesis independent of Apc-germline mutations, and reveal Pla2g2a target genes and pathways in non-pathologic colon microenvironment that influence conditions for colorectal cancer development.

scholarly journals A Novel Processing-Free Method for RNAseq Analysis of Spontaneous Sputum in Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Ricci ◽  
Michele Bassi ◽  
Cathy M. McGeough ◽  
Gera L. Jellema ◽  
Mirco Govoni
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Molecular Transport ◽  
Gene Set Enrichment Analysis ◽  
Induced Sputum ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Average Percentage ◽  
Non Invasive ◽  
Copd Patients

Background: Assessments of airways inflammation in patients with chronic obstructive pulmonary disease (COPD) require semi-invasive procedures and specialized sample processing know-how. In this study we aimed to set up and validate a novel non-invasive processing-free method for RNA sequencing (RNAseq) of spontaneous sputum samples collected from COPD patients.Methods: Spontaneous sputum samples were collected and stabilized, with or without selection of plugs and with or without the use of a stabilizer specifically formulated for downstream diagnostic testing (PrimeStore® Molecular Transport Medium). After 8 days storage at ambient temperature RNA was isolated according to an optimized RNAzol® method. An average percentage of fragments longer than 200 nucleotides (DV200) >30% and an individual yield >50 ng were required for progression of samples to sequencing. Finally, to assess if the transcriptome generated would reflect a true endotype of COPD inflammation, the outcome of single-sample gene-set enrichment analysis (ssGSEA) was validated using an independent set of processed induced sputum samples. Results: RNA extracted from spontaneous sputum using a stabilizer showed an average DV200 higher than 30%. 70% of the samples had a yield >50 ng and were submitted to downstream analysis. There was a straightforward correlation in terms of gene expression between samples handled with or without separation of plugs. This was also confirmed by principal component analysis and ssGSEA. The top ten enriched pathways resulting from spontaneous sputum ssGSEA were associated to features of COPD, namely, inflammation, immune responses and oxidative stress; up to 70% of these were in common within the top ten enriched pathways resulting from induced sputum ssGSEA.Conclusion: This analysis confirmed that the typical COPD endotype was represented within spontaneous sputum and supported the current method as a non-invasive processing-free procedure to assess the level of sputum cell inflammation in COPD patients by RNAseq analysis.

scholarly journals Expression Analysis of Muscle-Specific miRNAs in Plasma-Derived Extracellular Vesicles from Patients with Chronic Obstructive Pulmonary Disease

Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 502
Author(s):  
Sara Carpi ◽  
Beatrice Polini ◽  
Dario Nieri ◽  
Nevio Dubbini ◽  
Alessandro Celi ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Receiver Operating Characteristic ◽  
Pulmonary Disease ◽  
Extracellular Vesicles ◽  
Operating Characteristic ◽  
Expression Profiles ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Group B

MicroRNAs (miRNAs) are a class of short non-coding RNAs involved in the regulation of gene expression and the control of several cellular processes at physiological and pathological levels. Furthermore, extracellular vesicles (EV), which are small membrane-bound vesicles secreted by cells in the extracellular environment, contain functional miRNAs. The remarkable deregulation of many miRNAs has been demonstrated in respiratory diseases. Among them, miR-206, miR-133a-5p, and miR-133a-3p are striated muscle-specific miRNAs (myo-miRNA), related to skeletal muscle dysfunction, one of the commonest systemic manifestations in patients with chronic obstructive pulmonary disease (COPD). Nevertheless, their circulating expression in COPD patients is not demonstrated. For these reasons, we performed a pilot study to analyze the expression profiles of myo-miRNAs in plasma-derived EV from patients with COPD. We analyzed the expression profiles of selected myo-miRNAs in plasma-derived EV from COPD. Receiver operating characteristic analyses were carried out to evaluate whether selected plasma miRNAs were able to discriminate between different groups of COPD patients. We found EV-embedded myo-miRNAs in the bloodstream of COPD patients. Specifically, miR-206, miR-133a-5p and miR-133a-3p were significantly upregulated in group B patients. Receiver operating characteristic analyses of the combination of these selected miRNAs showed their high capacity to discriminate group B from other COPD patients. Our data provide evidence that myo-miRNA are present in EV in the plasma of COPD patients and their expression (miR-206, miR-133a-5p, and miR-133a-3p) can discriminate group B from group C patients. The future analysis of a larger number of patients should allow us to obtain more refined correlations.

scholarly journals Expression Profile Analysis Identifies Key Genes as Prognostic Markers for Metastasis of Osteosarcoma

2020 ◽  
Author(s):  
Xiaoqing Guan ◽  
Zhiyuan Guan ◽  
Jiafu Ji ◽  
Chunli Song
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Prognostic Markers ◽  
Profile Analysis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Gene Set Enrichment Analysis ◽  
Key Genes

Abstract Background : Osteosarcoma (OS) is the most common malignant tumor of bone which was featured with osteoid or immature bone produced by the malignant cells, and biomarkers are urgently needed to identify patients with this aggressive disease. Methods : We downloaded gene expression profiles from Gene Expression Omnibus (GEO) and The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) datasets for OS, respectively, and performed weighted gene co-expression network analysis (WGCNA) to identify the key module. Whereafter, functional annotation and Gene Set Enrichment Analysis (GSEA) demonstrated the relationships between target genes and OS. Results : In this study, we discovered four key genes – ALOX5AP, HLA-DMB, HLA-DRA and SPINT2 as new prognostic markers and confirmed their relationship with OS metastasis in the validation set. Conclusions : Overall, our work may shed light on the roles of ALOX5AP, HLA-DMB, HLA-DRA and SPINT2, thus providing valuable clues to investigate the metastasis of OS and corroborating the potential clinical application value of the 4-gene signature to some extent.

scholarly journals Determining Pharmacological Mechanisms of Chinese Incompatible Herbs Fuzi and Banxia in Chronic Obstructive Pulmonary Disease: A Systems Pharmacology-Based Study

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Kaiwen Ni ◽  
Xiaolu Cai ◽  
Yaling Chen ◽  
Linshui Zhou ◽  
Ruilin Chen ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Target Genes ◽  
Network Pharmacology ◽  
Chronic Obstructive ◽  
Healthy Individuals ◽  
Obstructive Pulmonary Disease ◽  
Pathway Network ◽  
Gene Pathway ◽  
Copd Patients

Aconiti Lateralis Radix Praeparata (Fuzi) and Pinelliae Rhizoma (Banxia) are among the 18 incompatible medications that are forbidden from use in one formulation. However, there is increasing evidence implying that this prohibition is not entirely correct. According to the theory of Chinese traditional medicine, they can be used for the treatment of chronic obstructive pulmonary disease (COPD). Thus, we analyzed the possible approaches for the treatment of COPD using network pharmacology. The active compounds of Fuzi and Banxia (FB) were collected, and their targets were identified. COPD-related targets were obtained by analyzing the differentially expressed genes between COPD patients and healthy individuals, which were expressed using a Venn diagram of COPD and FB. Protein-protein interaction data and network regarding COPD and drugs used were obtained. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted. The gene-pathway network was constructed to screen the key target genes. In total, 34 active compounds and 47 targets of FB were identified; moreover, 7,153 differentially expressed genes were identified between COPD patients and healthy individuals. The functional annotations of target genes were found to be related to mechanisms such as transcription, cytosol, and protein binding; furthermore, 68 pathways including neuroactive ligand-receptor interaction, Kaposi sarcoma-associated herpesvirus infection, apoptosis, and measles were significantly enriched. FOS CASP3, VEGFA, ESR1, and PTGS2 were the core genes in the gene-pathway network of FB for the treatment of COPD. Our results indicated that the effect of FB against COPD may involve the regulation of immunological function through several specific biological processes and their corresponding pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of herb-opponents FB.

Oral and Oropharyngeal Sensory Function in Adults With Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 29 (2) ◽  
pp. 864-872
Author(s):  
Fernanda Borowsky da Rosa ◽  
Adriane Schmidt Pasqualoto ◽  
Catriona M. Steele ◽  
Renata Mancopes
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Oral Cavity ◽  
Pulmonary Disease ◽  
Thermal Sensation ◽  
Sensory Function ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Copd Patients

Introduction The oral cavity and pharynx have a rich sensory system composed of specialized receptors. The integrity of oropharyngeal sensation is thought to be fundamental for safe and efficient swallowing. Chronic obstructive pulmonary disease (COPD) patients are at risk for oropharyngeal sensory impairment due to frequent use of inhaled medications and comorbidities including gastroesophageal reflux disease. Objective This study aimed to describe and compare oral and oropharyngeal sensory function measured using noninstrumental clinical methods in adults with COPD and healthy controls. Method Participants included 27 adults (18 men, nine women) with a diagnosis of COPD and a mean age of 66.56 years ( SD = 8.68). The control group comprised 11 healthy adults (five men, six women) with a mean age of 60.09 years ( SD = 11.57). Spirometry measures confirmed reduced functional expiratory volumes (% predicted) in the COPD patients compared to the control participants. All participants completed a case history interview and underwent clinical evaluation of oral and oropharyngeal sensation by a speech-language pathologist. The sensory evaluation explored the detection of tactile and temperature stimuli delivered by cotton swab to six locations in the oral cavity and two in the oropharynx as well as identification of the taste of stimuli administered in 5-ml boluses to the mouth. Analyses explored the frequencies of accurate responses regarding stimulus location, temperature and taste between groups, and between age groups (“≤ 65 years” and “> 65 years”) within the COPD cohort. Results We found significantly higher frequencies of reported use of inhaled medications ( p < .001) and xerostomia ( p = .003) in the COPD cohort. Oral cavity thermal sensation ( p = .009) was reduced in the COPD participants, and a significant age-related decline in gustatory sensation was found in the COPD group ( p = .018). Conclusion This study found that most of the measures of oral and oropharyngeal sensation remained intact in the COPD group. Oral thermal sensation was impaired in individuals with COPD, and reduced gustatory sensation was observed in the older COPD participants. Possible links between these results and the use of inhaled medication by individuals with COPD are discussed.

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