Analysis of protein-protein interaction network in chronic obstructive pulmonary disease

Yuan, Yaping; Shi, Yanwei; Gu, Wenchao

doi:10.4238/2014.october.31.1

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…We detected association of 20 genes to higher susceptibility for COPD. Our findings on the association of SNPs located on ADAM19 (rs1422795) and KIT (rs3822214) to higher COPD susceptibility replicate the previous findings by other investigators [ 12 , 45 – 48 ]. The rs11048413 SNP on BHLHE41 causing an Ala298Val change have been associated to patient survival in lung adenocarcinoma.…”

Section: Discussionsupporting

confidence: 91%

A candidate gene identification strategy utilizing mouse to human big-data mining: “3R-tenet” in COPD genetic research

et al. 2018

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BackgroundEarly life impairments leading to lower lung function by adulthood are considered as risk factors for chronic obstructive pulmonary disease (COPD). Recently, we compared the lung transcriptomic profile between two mouse strains with extreme total lung capacities to identify plausible pulmonary function determining genes using microarray analysis (GSE80078). Advancement of high-throughput techniques like deep sequencing (eg. RNA-seq) and microarray have resulted in an explosion of genomic data in the online public repositories which however remains under-exploited. Strategic curation of publicly available genomic data with a mouse-human translational approach can effectively implement “3R- Tenet” by reducing screening experiments with animals and performing mechanistic studies using physiologically relevant in vitro model systems. Therefore, we sought to analyze the association of functional variations within human orthologs of mouse lung function candidate genes in a publicly available COPD lung RNA-seq data-set.MethodsAssociation of missense single nucleotide polymorphisms, insertions, deletions, and splice junction variants were analyzed for susceptibility to COPD using RNA-seq data of a Korean population (GSE57148). Expression of the associated genes were studied using the Gene Paint (mouse embryo) and Human Protein Atlas (normal adult human lung) databases. The genes were also assessed for replication of the associations and expression in COPD−/mouse cigarette smoke exposed lung tissues using other datasets.ResultsSignificant association (p < 0.05) of variations in 20 genes to higher COPD susceptibility have been detected within the investigated cohort. Association of HJURP, MCRS1 and TLR8 are novel in relation to COPD. The associated ADAM19 and KIT loci have been reported earlier. The remaining 15 genes have also been previously associated to COPD. Differential transcript expression levels of the associated genes in COPD- and/ or mouse emphysematous lung tissues have been detected.ConclusionOur findings suggest strategic mouse-human datamining approaches can identify novel COPD candidate genes using existing datasets in the online repositories. The candidates can be further evaluated for mechanistic role through in vitro studies using appropriate primary cells/cell lines. Functional studies can be limited to transgenic animal models of only well supported candidate genes. This approach will lead to a significant reduction of animal experimentation in respiratory research.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0795-y) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 91%

A candidate gene identification strategy utilizing mouse to human big-data mining: “3R-tenet” in COPD genetic research

et al. 2018

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“…29 In the PPI network, several genes (such as DDX3Y) associated with COPD were identified. 19 By augmenting the level of DDX5, the expression of miR-183, miR-146b and miR-23b in hepar cells was suppressed by COX-2. 30 However, there are few reports about the influence of DDX3Y on COPD and the relationship between DDX3Y and miR-497.…”

Section: Discussionmentioning

confidence: 99%

“…GSE106986) ( Figure 3A). Based on comprehensive literature analyses, 19 DDX3Y was selected as a target of miR-497 for further study. Analysis of GSE106986 data set showed that DDX3Y mRNA expression level was visibly higher in COPD patients (n = 14) than that in normal samples (n = 5) ( Figure 3B).…”

Section: The Expression Level Of Ddx3y In Copd Patientsmentioning

confidence: 99%

“…9 In addition to the key genes related to COPD pathogenesis, non-coding RNAs containing microRNAs (miRNAs) have been shown to be concerned with COPD. 10,11 miRNAs, with [19][20][21][22][23][24][25] nucleotides, are a series of small endogenous nucleotide RNAs that participate in various biological processes by negatively modulate genes expression under post-transcriptional level. 12,13 The dysregulation of miRNAs are involved in multifarious diseases including COPD, which are often utilized as biomarkers for exposure to environmental factors.…”

Section: Introductionmentioning

confidence: 99%

“…DDX3Y encodes an RNA helicase of the big DDX3 subfamily of the DEAD-box family of proteins 27. In the PPI network, several genes (such as DDX3Y) associated with COPD were identified 19. By reprogramming the chromosomes specifically, DDX3X and DDX3Y are localized to the non-recombinant portions of both sex chromosomes 29.…”

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confidence: 99%

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MicroRNA‐497 functions as an inflammatory suppressor via targeting DDX3Y and modulating toll‐like receptor 4/NF‐κB in cigarette smoke extract‐stimulated human bronchial epithelial cells

Jia

Zhao

2019

The Journal of Gene Medicine

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Background:We aimed to investigate the biological effect of miR-497 in cigarette smoke extract (CSE)-damaged human bronchial epithelial (HBE) cells and the underlying molecular mechanism.Methods: MiR-497 mimic was transfected into HBE cells to up-regulate miR-497 expression. Cigarette smoke extract (CSE, 20 μg/mL) was utilized to treat HBE cells to form the injury model. Cell proliferation and apoptosis were detected by CCK8 and flow cytometry assays. DDX3Y mRNA expression was determined by a quantitative reverse transcriptase-polymerase chain reaction. The interaction between miR-497 and DDX3Y was verified by a luciferase reporter assay. Protein expression levels were tested by western blotting.Results: CSE treatment decreased miR-497 level in HBE cells. CSE exposure restrained cell proliferation, promoted cell apoptosis and enhanced the relative expression of TLR4 and p-NF-κB p65. DDX3Y was predicted as a target of miR-497. The mRNA and protein expression of DDX3Y was negatively modulated by miR-497 in CSE-injured HBE cells. Up-regulation of miR-497 by miR-497 mimic increased cell proliferation and reduced cell apoptosis in CSE-treated HBE cells, which were rescued by DDX3Y high expression in CSE-treated HBE cells. Consistently, Bcl-2 protein level was heightened, whereas Bax and actived caspase-3/9 protein levels were decreased by miR-497 mimic in CSE-stimulated HBE cells, which was reversed by DDX3Y over-expression in CSE-stimulated HBE cells. The relative expression of TLR4 and p-NF-κB p65 was decreased by miR-497 mimic, whereas they were rescued by DDX3Y over-expression in CSE-damaged HBE cells. Conclusions:The results of the present study demonstrate that up-regulation of miR-497 exhibits a protective effect on CSE-damaged HBE cells, which might be achieved by targeting DDX3Y and regulating the TLR4/NF-κB pathway. KEYWORDSchronic obstructive pulmonary disease, cigarette smoke extract, DEAD-box helicase 3 Y-linked, human bronchial epithelial cells, miR-497, Toll-like receptor 4/NF-ĸB pathway

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KIT as a therapeutic target for non-oncological diseases

Martínez-Antón

Gras

Bourdin

et al. 2019

Pharmacology & Therapeutics

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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Analysis of protein-protein interaction network in chronic obstructive pulmonary disease

Cited by 7 publications

References 30 publications

A candidate gene identification strategy utilizing mouse to human big-data mining: “3R-tenet” in COPD genetic research

A candidate gene identification strategy utilizing mouse to human big-data mining: “3R-tenet” in COPD genetic research

MicroRNA‐497 functions as an inflammatory suppressor via targeting DDX3Y and modulating toll‐like receptor 4/NF‐κB in cigarette smoke extract‐stimulated human bronchial epithelial cells

KIT as a therapeutic target for non-oncological diseases

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