Development of microRNA expression signature for emphysema in COPD patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: santiyagu savarimuthu francis
PROVIDER: E-GEOD-33336 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:To define the role of microRNAs and their mRNA targets in emphysema severity in COPD patients. We performed Agilent human miRNA oligo arrays (8x15K array, Part No. G4470A, Agilent Technologies) based on miRBase V9.1 on lung tissues from 9 mild and 20 moderate emphysema lungs obtained from patients undergoing curative resection for lung cancer. We identified 5 miRNAs and two of those were tested and validated technically using qRT-PCR. The predicted mRNA targets for the five miRNAs were identified in MSigDB using GSEA and their expression were negatively correlated in exvivo lung mRNA expression profile obtained from GEO datasets (GSE17770 and GSE1650). Increasing the expression of one of the miRNA target, miR-34c in BEAS-2B and HFL 1 cell lines resulted in the downregulation of 50 TargetScan and Pictar predicted targets of miR-34c.
2012-05-31 | E-GEOD-33337 | biostudies-arrayexpress
Project description:Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by varying degrees of emphysematous lung destruction and small airway disease, each with distinct effects on clinical outcomes. There is little known about how microRNAs contribute specifically to the emphysema phenotype. We examined how microRNA expression is altered with regional emphysema severity within the lung and how these microRNAs regulate disease-associated gene-expression networks. Results: We profiled microRNAs in different regions in the lung with varying degrees of emphysema from 6 smokers with COPD and 2 controls (8 regions x 8 lungs = 64 samples). 63 microRNAs (p<0.05) were altered with regional emphysema severity as quantified by mean linear intercept (Lm). MicroRNA and gene expression data were then integrated in the same samples. A subset of microRNAs, including miR-638, miR-30c, and miR-181d, correlated with many of their predicted gene targets, suggesting a role in regulating the gene networks that underlie emphysematous lung destruction. Modulating miR-638 expression in primary human lung fibroblasts recapitulated the alterations in its targeted gene-expression network associated with emphysema progression. Pathway analysis revealed that genes involved in oxidative stress and accelerated aging were affected by miR-638 knock-down in fibroblasts. Many miR-638 gene targets in these pathways were amongst those negatively correlated with miR-638 expression in emphysematous lung tissue. Conclusions: Our findings demonstrate that microRNAs are altered with regional emphysema severity and modulate disease-associated gene expression networks. Furthermore, miR-638 may regulate gene expression associated with the oxidative stress response and aging in emphysematous lung tissue and fibroblasts. Paired samples were obtained from 8 regions at regular intervals between the apex and base of each explanted lung from six patients with severe COPD and two donors. The degree of emphysematous destruction was quantified in one sample from each region by mean linear intercept (Lm), while microRNA expression was profiled in the adjacent sample from the same region using the NCode Version 3 microRNA microarrays (Invitrogen, Carlsbad, CA). After quality control 60 samples were used for the analysis.
2013-12-31 | E-GEOD-49881 | biostudies-arrayexpress
Project description:Combined pulmonary fibrosis and emphysema (CPFE) is characterized by upper-lobe emphysema combined with lower-lobe fibrosis and a high prevalence of pulmonary hypertension. The aim of this study was to measure and analyze gene expression profiles in the lungs of CPFE patients. The results showed that the expression profiles of the fibrotic and emphysematous lesions were remarkably different in terms of function. Genes related to immune system, structural constituents of cytoskeleton, and cellular adhesion were overexpressed in fibrotic lesions, while genes associated with cellular fraction, cell membrane structures, vascular growth and biology, second-messenger-mediated signaling, and lung development (all processes that contribute to the destruction and repair of cells, vessels, and lung) were overexpressed in emphysematous lesions. The differences in gene expression were detected in fibrotic and emphysematous lesions in CPFE patients. We propose that the development of coexisted fibrotic and emphysematous lesions in CPFE is implemented by these different patterns of gene expressions. Lung tissue specimens from fibrous lesions and emphysematous lesions of 3 patients with combined pulmonary fibrosis and emphysema (CPFE) were obtained for RNA extraction and hybridization on Affymetrix microarrays. We hypothesized that coexisted fibrosis and emphysema in CPFE are programmed by differential gene expressions in the corresponding lesions in the lungs of smokers susceptible to CPFE. Given the importance of genetic susceptibility in understanding the etiology and pathogenesis of CPFE, we examined tissues from patients with CPFE to systemically identify genes significantly expressed in lung tissues with fibrotic lesions as well as genes significantly expressed in tissues with emphysematous lesions.
2012-06-26 | E-GEOD-38934 | biostudies-arrayexpress
Project description:Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by varying degrees of emphysematous lung destruction and small airway disease, each with distinct effects on clinical outcomes. There is little known about how microRNAs contribute specifically to the emphysema phenotype. We examined how microRNA expression is altered with regional emphysema severity within the lung and how these microRNAs regulate disease-associated gene-expression networks. Results: We profiled microRNAs in different regions in the lung with varying degrees of emphysema from 6 smokers with COPD and 2 controls (8 regions x 8 lungs = 64 samples). 63 microRNAs (p<0.05) were altered with regional emphysema severity as quantified by mean linear intercept (Lm). MicroRNA and gene expression data were then integrated in the same samples. A subset of microRNAs, including miR-638, miR-30c, and miR-181d, correlated with many of their predicted gene targets, suggesting a role in regulating the gene networks that underlie emphysematous lung destruction. Modulating miR-638 expression in primary human lung fibroblasts recapitulated the alterations in its targeted gene-expression network associated with emphysema progression. Pathway analysis revealed that genes involved in oxidative stress and accelerated aging were affected by miR-638 knock-down in fibroblasts. Many miR-638 gene targets in these pathways were amongst those negatively correlated with miR-638 expression in emphysematous lung tissue. Conclusions: Our findings demonstrate that microRNAs are altered with regional emphysema severity and modulate disease-associated gene expression networks. Furthermore, miR-638 may regulate gene expression associated with the oxidative stress response and aging in emphysematous lung tissue and fibroblasts.
2013-12-31 | GSE49881 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE33336: Development of microRNA expression signature for emphysema in COPD patients GSE33337: miRNA changes in mild and moderate emphysema correlate with target gene expression in vivo and in vitro [target gene expression data] Refer to individual Series
2012-05-31 | E-GEOD-33338 | biostudies-arrayexpress
Project description:Analysis of lung CD11c+ antigen presenting cells (APCs) isolated from wildtype or Mir22-/- mice exposed to nanoparticulate carbon black (nCB) for one month. MiR-22 plays important roles in nCB induced experimental emphysema through regulating APC activation. Results provide insight into the biological role and target genes of miR-22. Smoking-related emphysema is a chronic inflammatory disease driven by T helper 17 (TH17) cells through molecular mechanisms that remain obscure. Here we have explored the role of microRNA-22 (miR-22) in emphysema. MiR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism involving NF-kappaB. MiR-22-deficient mice, but not wild-type, showed attenuated TH17 responses and failed to develop emphysema after exposure to either smoke or nCB. We further show that miR-22 controls APC activation and TH17 responses through activation of AP-1 transcription factor complexes and histone deacetylase (HDAC) 4. Thus, miR-22 is a critical regulator of both emphysema and TH17 responses. Lung APCs were isolated from PBS (reference groups) or nCB exposed wildtype or Mir22-/- mice, total four groups. There were three replicates in each group.
2015-09-05 | E-GEOD-72734 | biostudies-arrayexpress
Project description:Lung myeloid dendritic cells isolated from emphysema but not healthy subjects induce Th1 and Th17 cells differentiation. The goal of this study is to identify the genes differentially expressed by lung myeloid dendritic cells from healthy or emphysema subjects. These genes may play crucial roles in directing Th1 and Th17 cells differentiation. Total mRNA was extracted from lung myeloid dendritic cells isolated from lungs of three healthy controls and three emphysema patients.
2011-01-01 | E-GEOD-26296 | biostudies-arrayexpress
Project description:Persistent pulmonary hypertension of the newborn (PPHN) occurs when pulmonary vascular resistance (PVR) fails to decrease at birth. Decreased angiogenesis in the lung contributes to the persistence of high PVR at birth. MicroRNAs (miRNAs) regulate gene expression through transcript binding and degradation. They were implicated in dysregulated angiogenesis in cancer and cardiovascular disease. We investigated whether altered miRNA levels contribute to impaired angiogenesis in PPHN. We used a fetal lamb model of PPHN induced by prenatal ductus arteriosus constriction and sham ligation as controls. We performed RNA sequencing of pulmonary artery endothelial cells (PAECs) isolated from control and PPHN lambs. We observed a differentially expressed miRNA profile in PPHN for organ development, cell-cell signaling, and cardiovascular function. MiR-34c was upregulated in PPHN PAECs compared to controls. Exogenous miR34c mimics decreased angiogenesis by control PAEC and anti-miR34c improved angiogenesis of PPHN PAEC in vitro. Notch1, a predicted target for miR-34c by bioinformatics, was decreased in PPHN PAECs, along with Notch1 downstream targets, Hey1 and Hes1. Exogenous miR-34c decreased Notch1 expression in control PAECs and anti-miR-34c restored Notch1 and Hes1 expression in PPHN PAECs. We conclude that increased miR-34c in PPHN contributes to impaired angiogenesis by decreasing Notch1 expression in PAECs."
2022-08-26 | GSE211867 | GEO
Project description:Type II cell differentiation and expression of the major surfactant protein, SP-A, in midgestation human fetal lung (HFL) are markedly induced by cAMP and inhibited by TGF-β. cAMP induction of SP-A promoter activity is mediated by increased phosphorylation and in vivo binding of TTF-1/Nkx2.1, a critical transcription factor in lung development. To further define mechanisms for developmental induction of surfactant synthesis in HFL, herein, we investigated the potential role of microRNAs (miRNAs, miRs). To identify and characterize differentially regulated miRNAs in mid-gestation HFL explants during type II pneumocyte differentiation in culture, we performed miRNA microarray analysis of RNA isolated from epithelial cells from midgestation HFL explants before and after culture ± Bt2cAMP. Interestingly, the miR-200 family was significantly upregulated during type II cell differentiation; miR-200 family induction was inversely correlated with expression of its known targets, transcription factors ZEB1 and ZEB2, and TGF-b2. miR-200 antagonists inhibited TTF-1 and SP-A expression and upregulated TGF-β2 and ZEB1 expression in type II cells. Overexpression of ZEB1 in cultured type II cells decreased DNA binding of endogenous TTF-1, blocked cAMP stimulation of SP-A and inhibited miR-200 expression,whereas, cAMP markedly inhibited ZEB1/2 and TGF-β. Importantly, overexpression of ZEB1 or miR-200 antagonists in HFL type II cells markedly suppressed accumulation of lamellar bodies, organelles that store surfactant. Our findings suggest that the miR-200 family and ZEB1, which exist in a double-negative feedback loop regulated by TGF-β, serve important regulatory roles in the developmental regulation of type II cell differentiation and SP-A expression in HFL.
2015-10-01 | GSE61183 | GEO