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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Integrative meta-analysis identifies microRNA-regulated networks in infantile hemangioma
Natália Bertoni1, Lied M S Pereira2, Fábio E Severino3
1Department of Surgery and Orthopedics, Faculty of Medicine, São Paulo State University-UNESP, Av. Prof. Montenegro, 18618-970, Botucatu, São Paulo, Brazil. bertoni.na@gmail.com.
Background:
Hemangioma is a common benign tumor in the childhood; however our knowledge about the molecular mechanisms of hemangioma development and progression are still limited. Currently, microRNAs (miRNAs) have been shown as gene expression regulators with an important role in disease pathogenesis. Our goals were to identify miRNA-mRNA expression networks associated with infantile hemangioma.
Methods:
We performed a meta-analysis of previously published gene expression datasets including 98 hemangioma samples. Deregulated genes were further used to identify microRNAs as potential regulators of gene expression in infantile hemangioma. Data were integrated using bioinformatics methods, and genes were mapped in proteins, which were then used to construct protein-protein interaction networks.
Results:
Deregulated genes play roles in cell growth and differentiation, cell signaling, angiogenesis and vasculogenesis. Regulatory networks identified included microRNAs miR-9, miR-939 and let-7 family; these microRNAs showed the most number of interactions with deregulated genes in infantile hemangioma, suggesting that they may have an important role in the molecular mechanisms of disease. Additionally, results were used to identify drug-gene interactions and druggable gene categories using Drug-Gene Interaction Database. We show that microRNAs and microRNA-target genes may be useful biomarkers for the development of novel therapeutic strategies for patients with infantile hemangioma.
Conclusions:
microRNA-regulated pathways may play a role in infantile hemangioma development and progression and may be potentially useful for future development of novel therapeutic strategies for patients with infantile hemangioma.
Insights
This study reveals key microRNAs (miRNAs) involved in infantile hemangioma development. These miRNA-mRNA networks offer potential biomarkers for new therapeutic strategies against this common childhood tumor.
Area of Science:
- Pediatric Oncology
- Molecular Biology
- Bioinformatics
Background:
- Infantile hemangioma is a prevalent pediatric tumor with poorly understood molecular underpinnings.
- MicroRNAs (miRNAs) are critical regulators of gene expression implicated in various disease pathologies.
- Understanding miRNA involvement is crucial for elucidating hemangioma pathogenesis.
Purpose of the Study:
- To identify microRNA-messenger RNA (mRNA) expression networks associated with infantile hemangioma.
- To explore the role of specific miRNAs in the molecular mechanisms of hemangioma development and progression.
Main Methods:
- Conducted a meta-analysis of 98 infantile hemangioma gene expression datasets.
- Employed bioinformatics to identify deregulated genes and potential miRNA regulators.
- Constructed protein-protein interaction networks and analyzed drug-gene interactions.
Main Results:
- Identified deregulated genes crucial for cell growth, differentiation, angiogenesis, and vasculogenesis.
- Uncovered significant interactions involving miR-9, miR-939, and the let-7 family of miRNAs.
- Highlighted potential drug-gene interactions and druggable gene categories.
Conclusions:
- MicroRNA-regulated pathways are implicated in infantile hemangioma pathogenesis.
- Identified miRNAs and their target genes may serve as valuable biomarkers.
- These findings pave the way for developing novel therapeutic strategies for infantile hemangioma.
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