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Published on: August 7, 2017
Peripheral blood miRNAs are associated with airflow below threshold in children with asthma
Anshul Tiwari1,2, Brian D Hobbs1,3, Rinku Sharma1
1Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Background:
MicroRNAs (miRNAs) are crucial post-transcriptional regulators involved in inflammatory diseases, such as asthma. Poor lung function and airflow issues in childhood are linked to the development of chronic obstructive pulmonary disease (COPD) in adulthood.
Methods:
We analyzed small RNA-Seq data from 365 peripheral whole blood samples from the Genetics of Asthma in Costa Rica Study (GACRS) for association with airflow levels measured by FEV1/FVC. Differentially expressed (DE) miRNAs were identified using DESeq2 in R, adjusting for covariates and applying a 10% false discovery rate (FDR). The analysis included 361 samples and 649 miRNAs. The two DE miRNAs were further tested for association with airflow obstruction in a study of adult former smokers with and without COPD.
Results:
We found 1 upregulated and 1 downregulated miRNA in participants with airflow below the threshold compared to those above it. In the adult study, the same miRNAs were upregulated and downregulated in individuals with FEV1/FVC < 0.7 versus those with FEV1/FVC > 0.7, showing suggestive statistical evidence. The target genes of these miRNAs were enriched for PI3K-Akt, Hippo, WNT, MAPK, and focal adhesion pathways.
Conclusions:
Two differentially expressed miRNAs were associated with airflow levels in children with asthma and airflow obstruction in adults with COPD. This suggests that shared genetic regulatory systems may influence childhood airflow and contribute to adulthood airflow obstruction.
Insights
Two microRNAs (miRNAs) linked to childhood asthma also appear in adults with COPD, suggesting shared genetic regulation of lung function across lifespans. These findings highlight potential biomarkers for airflow obstruction.
Area of Science:
- Genomics
- Pulmonary Medicine
- Molecular Biology
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression implicated in inflammatory conditions like asthma.
- Childhood airflow obstruction is a predictor for developing chronic obstructive pulmonary disease (COPD) later in life.
Purpose of the Study:
- To investigate the association between microRNAs (miRNAs) and airflow obstruction in children with asthma.
- To determine if identified miRNAs are also linked to airflow obstruction in adults with COPD.
Main Methods:
- Small RNA sequencing data from 365 children in the Genetics of Asthma in Costa Rica Study (GACRS) were analyzed for differential expression of miRNAs related to FEV1/FVC ratios.
- Statistical analysis using DESeq2 in R identified differentially expressed miRNAs, adjusting for covariates and controlling the false discovery rate (FDR).
- Two significant miRNAs were further validated in a separate cohort of adult former smokers with and without COPD.
Main Results:
- One miRNA was found to be upregulated and another downregulated in children with lower airflow compared to those with normal airflow.
- The same miRNA expression patterns were observed in adults with COPD (FEV1/FVC < 0.7) compared to controls.
- Pathway analysis indicated that target genes of these miRNAs are involved in critical signaling pathways, including PI3K-Akt, Hippo, WNT, MAPK, and focal adhesion.
Conclusions:
- Two differentially expressed miRNAs are associated with airflow parameters in both pediatric asthma and adult COPD.
- These findings suggest a potential shared genetic regulatory mechanism influencing lung function from childhood through adulthood.
- The identified miRNAs may serve as biomarkers for airflow obstruction and could offer therapeutic targets.
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