Circulating MicroRNAs and Treatment Response in Childhood Asthma
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ABSTRACT:
PROVIDER: PRJNA556710 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9837070.fastq.gz | Fastqsanger.gz | |||
| SRR9837080.fastq.gz | Fastqsanger.gz | |||
| SRR9837090.fastq.gz | Fastqsanger.gz | |||
| SRR9837100.fastq.gz | Fastqsanger.gz | |||
| SRR9837110.fastq.gz | Fastqsanger.gz |
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Project description:Bronchial asthma is one of the most common respiratory diseases. Reversible airflow limitation, persistent airway inflammation and airway hyperresponsiveness, and air remodeling is its main characterization. The morbidity and mortality rates of asthma increase due to air pollution. MicroRNAs are small molecules that regulate gene expression playing a part in inflammatory diseases. The designed current study aims to compare and screen circulating microRNAs targeting LIGHT as diagnostic biomarkers during asthma attack through microRNA microarray and Real Time PCR assay. Methods: Serum from 40 patients with asthma attack and 20 normal subjects was collected to detect circulating microRNAs expression profile through miRNA microarray. It is revealed that the significant differences of microRNAs level between asthmatic patients and normal controls. Target gene predictive analysis of differentially expressing microRNAs was performed to screen the miRNAs targeting LIGHT gene basing on the TargetScan bioinformatics software. Real Time PCR was conducted to further verify the realiability of the miRNA microassay and the screened specific miRNAs targeting LIGHT. Results: Asthmatic patients had a significant upper expression of miR-512-3p, miR-513b-5p, miR-5691 and lower level of miR-107, miR-140-5p, miR-17-5p compared with healthy subjects. The level of miR-140-5p and miR-107 in plasma of asthmatic patients were tightly correlated with their eosinophilic inflammation. The plasma miR-140-5p and miR-107 were needed to perform further investigation to evaluate the role as biomarkers in diagnosis of asthma.
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Project description:We aimed to apply microRNA to explore the underlying mechanism of nonallergic childhood asthma
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Project description:Rationale: Inhaled corticosteroids (ICS) are key treatments for controlling asthma and preventing asthma attacks. However, the responsiveness to ICS varies among individuals. MicroRNAs (miRNAs) have been lauded for their prognostic utility.Objectives: We hypothesized that circulating miRNAs obtained at baseline/prerandomization in the Childhood Asthma Management Program (CAMP) could serve as biomarkers and biologic mediators of ICS clinical response over the 4-year clinical trial period.Methods: We selected baseline serum samples from 462 CAMP subjects subsequently randomized to either ICS (budesonide) or placebo. Samples underwent small RNA sequencing, and read counts were normalized and filtered by depth and coverage. Linear regression was used to associate miRNAs with change in FEV1% (prebronchodilator FEV1 as a percent predicted) over the 4-year treatment period in both main effects and interaction models. We validated the function of the top associated miRNAs by luciferase reporter assays of glucocorticoid-mediated transrepression and predicted response to ICS through logistic regression models.Measurements and Main Results: We identified 7 miRNAs significantly associated with FEV1% change (P ≤ 0.05) and 15 miRNAs with significant interaction (P ≤ 0.05) to ICS versus placebo treatments. We selected three miRNAs for functional validation, of which hsa-miR-155-5p and hsa-miR-532-5p were significantly associated with changes in dexamethasone-induced transrepression of NF-κB. Combined, these two miRNAs were predictive of ICS response over the course of the clinical trial, with an area under the receiver operating characteristic curve of 0.86.Conclusions: We identified two functional circulating miRNAs predictive of asthma ICS treatment response over time.
| S-EPMC7328325 | biostudies-literature
Project description:Total RNA was isolated from serum samples by the Qiagen miRNeasy Serum/Plasma extraction kit and QIAcube automation. All samples were quantified using the Nanodrop spectrophotometer prior to plating. Small RNA-seq libraries were prepared using the Norgen Biotek Small RNA Library Prep Kit and then sequenced on the Illumina NextSeq 500 platform at 51bp single end reads. ExceRpt was employed to assess the read quality and annotate miRNAs. The read count was log transformed and normalized by quantile normalization.
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Project description:Blood serum from 160 Childhood Asthma Management Program (CAMP) subjects were microRNA profiles with 13 subjects profiled twice. Each subject has diverse clinical phenotypes notably spirometry related phenotypes.
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Project description:Blood serum from 160 Childhood Asthma Management Program (CAMP) subjects were microRNA profiles with 13 subjects profiled twice. Each subject has diverse clinical phenotypes notably spirometry related phenotypes. Least squares linear regression was applied with subject phenotypes as the dependent variable, and microRNA Ct values (data matrix quantile normalized) as the independent variable to identify significant associations between subject phenotype and microRNA abundance.
2016-06-09 | E-GEOD-74770 | biostudies-arrayexpress
Project description:Profiling miRNA expression in cells that directly contribute to human disease pathogenesis is likely to aid the discovery of novel drug targets and biomarkers. However, tissue heterogeneity and the limited amount of human diseased tissue available for research purposes present fundamental difficulties that often constrain the scope and potential of such studies. We established a flow cytometry-based method for isolating pure populations of pathogenic T cells from bronchial biopsy samples of asthma patients, and optimized a high-throughput nano-scale qRT-PCR method capable of accurately measuring 96 miRNAs in as little as 100 cells. Comparison of circulating and airway T cells from healthy and asthmatic subjects revealed asthma-associated and tissue-specific miRNA expression patterns. These results establish the feasibility and utility of investigating miRNA expression in small populations of cells involved in asthma pathogenesis, and set a precedent for application of our nano-scale approach in other human diseases. We analyzed the concordance in results obtained by nano-scale qPCR and miRNA microarrays. RNA extracted from human Th2 cells was used for parallel profiling by both nano-scale PCR and microarray method. Fifty nanograms (ng) of RNA was used for the microarray method and cDNA from 1 ng (~1000 cell equivalent) of RNA, pre-amplified by 18 cycle PCR reaction, was used for miRNA detection by the nano-scale qPCR method (G.Seumois et al. in submission). Out of the 92 miRNAs assayed, 51 were detected by nano-scale qPCR. Of these, 45 were detected by microarray analysis, including the 32 miRNAs with the strongest signal intensities on the nano-scale qPCR platform. One sample; one color design. This is a single array from a larger normalized set of data investigating targeting microRNAs for asthma treatment that is to published separately.
2013-01-11 | E-GEOD-31030 | biostudies-arrayexpress
Project description:Asthma is caused by a combination of poorly understood genetic and environmental factors. We found multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in EBV-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P <10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encode transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma. Experiment Overall Design: Gene expression levels were evaluated in 404 children. We then evaluated the relationship between SNPs in the 17q21 region (which show association to asthma in the same children) with gene expression levels. See http://www.sph.umich.edu/csg/liang/asthma/
2007-11-09 | E-GEOD-8052 | biostudies-arrayexpress
Project description:Asthma is caused by a combination of poorly understood genetic and environmental factors. We found multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in EBV-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P <10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encode transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma. Keywords: association study, global gene expression, asthma, ORMDL3
2007-07-01 | GSE8052 | GEO