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Tissue-specific miRNA Expression Profiling in Mouse Heart Sections Using In Situ Hybridization
Published on: September 15, 2018
MicroRNA Clusters in the Adult Mouse Heart: Age-Associated Changes
Xiaomin Zhang1, Gohar Azhar1, Emmanuel D Williams1
1Reynolds Institute on Aging and Department of Geriatrics, University of Arkansas for Medical Science, 4301 West Markham Street, No. 748, Little Rock, AR 72205, USA ; Geriatric Research Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA.
Abstract:
The microRNAs and microRNA clusters have been implicated in normal cardiac development and also disease, including cardiac hypertrophy, cardiomyopathy, heart failure, and arrhythmias. Since a microRNA cluster has from two to dozens of microRNAs, the expression of a microRNA cluster could have a substantial impact on its target genes. In the present study, the configuration and distribution of microRNA clusters in the mouse genome were examined at various inter-microRNA distances. Three important microRNA clusters that are significantly impacted during adult cardiac aging, the miR-17-92, miR-106a-363, and miR-106b-25, were also examined in terms of their genomic location, RNA transcript character, sequence homology, and their relationship with the corresponding microRNA families. Multiple microRNAs derived from the three clusters potentially target various protein components of the cdc42-SRF signaling pathway, which regulates cytoskeleton dynamics associated with cardiac structure and function. The data indicate that aging impacted the expression of both guide and passenger strands of the microRNA clusters; nutrient stress also affected the expression of the three microRNA clusters. The miR-17-92, miR-106a-363, and miR-106b-25 clusters are likely to impact the Cdc42-SRF signaling pathway and thereby affect cardiac morphology and function during pathological conditions and the aging process.
Insights
MicroRNA clusters, including miR-17-92, miR-106a-363, and miR-106b-25, impact cardiac aging and function by targeting the Cdc42-SRF pathway. Nutrient stress and aging affect microRNA cluster expression, influencing heart health.
Area of Science:
- Genomics
- Molecular Biology
- Cardiovascular Research
Background:
- MicroRNAs (miRNAs) and miRNA clusters are crucial in cardiac development and disease.
- Dysregulation of miRNA clusters is linked to cardiac hypertrophy, cardiomyopathy, heart failure, and arrhythmias.
- miRNA clusters, containing multiple miRNAs, can significantly influence target gene expression.
Purpose of the Study:
- To examine the configuration and distribution of miRNA clusters in the mouse genome.
- To investigate three specific miRNA clusters (miR-17-92, miR-106a-363, miR-106b-25) impacted by cardiac aging.
- To explore the relationship between these miRNA clusters, the Cdc42-SRF signaling pathway, and cardiac function during aging and stress.
Main Methods:
- Genomic analysis of miRNA cluster configuration and distribution.
- Examination of RNA transcript character and sequence homology for key miRNA clusters.
- Assessment of miRNA cluster expression changes under aging and nutrient stress conditions.
Main Results:
- Aging significantly impacts the expression of both guide and passenger strands of the studied miRNA clusters.
- Nutrient stress also affects the expression of the miR-17-92, miR-106a-363, and miR-106b-25 clusters.
- Multiple miRNAs from these clusters potentially target proteins within the Cdc42-SRF signaling pathway.
Conclusions:
- The miR-17-92, miR-106a-363, and miR-106b-25 clusters are implicated in regulating the Cdc42-SRF pathway.
- These miRNA clusters likely influence cardiac morphology and function during aging and pathological conditions.
- Understanding these miRNA cluster dynamics offers insights into age-related cardiac dysfunction.
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