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Published on: August 7, 2017
COPD-associated miR-145-5p is downregulated in early-decline FEV1 trajectories in childhood asthma
Anshul Tiwari1, Jiang Li1, Alvin T Kho2
1Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
Insights
Reduced levels of miR-145-5p in children with asthma may predict early decline in lung function, a risk factor for developing chronic obstructive pulmonary disease (COPD). This finding highlights miR-145-5p as a potential early biomarker for COPD risk.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Biomarker Discovery
Background:
- MicroRNAs (miRNAs) are implicated in asthma and chronic obstructive pulmonary disease (COPD).
- Children with asthma exhibit diverse lung function growth trajectories, including reduced growth (RG) and early decline (ED), with some patterns linked to adverse outcomes like COPD.
Purpose of the Study:
- To investigate if circulating miRNAs in early childhood asthma can predict long-term lung function growth patterns over 16 years.
- To identify specific miRNAs associated with detrimental lung function trajectories.
Main Methods:
- Small RNA sequencing was performed on sera from 492 children (aged 5-12) with mild-to-moderate asthma.
- Differential expression analysis of miRNAs was conducted comparing distinct lung function growth patterns.
- In vitro studies assessed the role of identified miRNAs in airway smooth muscle cell growth.
Main Results:
- Analysis of 448 samples revealed hsa-miR-145-5p as significantly dysregulated (P < 8.01E-05) when comparing normal growth to the most severe group (RGED).
- This miRNA was downregulated in both early decline (ED) groups (ED and RGED).
- In vitro experiments confirmed hsa-miR-145-5p's association with airway smooth muscle cell proliferation.
Conclusions:
- Downregulation of miR-145-5p is associated with early decline lung function patterns in children with asthma, a precursor to COPD.
- miR-145-5p promotes airway smooth muscle cell proliferation, suggesting a mechanistic link to disease progression.
- Reduced miR-145-5p expression may serve as a significant risk factor for long-term lung function decline and COPD development.
Background:
Many microRNAs (miRNAs) have been associated with asthma and chronic obstructive pulmonary disease (COPD). Longitudinal lung function growth trajectories of children with asthma-normal growth, reduced growth (RG), early decline (ED), and RG with an ED (RGED)-have been observed, with RG and RGED associated with adverse outcomes, including COPD.
Objective:
Our aim was to determine whether circulating miRNAs from an early age in children with asthma would be prognostic of reduced lung function growth patterns over the next 16 years.
Methods:
We performed small RNA sequencing on sera from 492 children aged 5 to 12 years with mild-to-moderate asthma from the CAMP clinical trial, who were subsequently followed for 12 to 16 years. miRNAs were assessed for differential expression between previously assigned lung function growth patterns.
Results:
We had 448 samples and 259 miRNAs for differential analysis. In a comparison of the normal and the most severe group (ie, normal growth compared with RGED), we found 1 strongly dysregulated miRNA, hsa-miR-145-5p (P < 8.01E-05). This miR was downregulated in both ED groups (ie, ED and RGED). We verified that miR-145-5p was strongly associated with airway smooth muscle cell growth in vitro.
Conclusion:
Our results showed that miR-145-5p is associated with the ED patterns of lung function growth leading to COPD in children with asthma and additionally increases airway smooth muscle cell proliferation. This represents a significant extension of our understanding of the role of miR-145-5p in COPD and suggests that reduced expression of miR-145-5p is a risk factor for ED of long-term lung function.
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