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Published on: April 10, 2018
Long Noncoding RNAs and Their Regulatory Network: Potential Therapeutic Targets for Adult Moyamoya Disease
Faliang Gao1, Lanbing Yu1, Dong Zhang1
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China; China National Clinical Research Center for Neurological Diseases, Beijing, P. R. China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, P. R. China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, P. R. China.
Objective:
To investigate long noncoding ribonucleic acid (lncRNA) expression patterns in adult moyamoya disease (MMD) patients and explore their possible roles in the pathophysiology of MMD.
Methods:
A healthy control group (n = 10) and an MMD group (n = 15) were evaluated. RNA was extracted from peripheral blood samples and hybridized to microarray to get lncRNA expression profiles. Then predicted lncRNA target genes were identified, and bioinformatics analysis was performed to investigate their molecular functions.
Results:
In the MMD group, 3649 lncRNAs exhibited more than 2-fold expression than their counterparts in the healthy control group; of these, 1494 were upregulated, while 2155 were downregulated. Principal component analysis and Hclust analysis produced completely different clusters between the 2 groups. Gene ontology and KEGG pathway enrichment analysis suggested that the differentially expressed lncRNAs regulate multiple signaling pathways that were related with inflammation and vascular disease, and mitogen-activated protein kinase (MAPK) signaling pathway was the core regulatory pathway.
Conclusions:
Long noncoding RNA expression profiles were quite different between MMD and control groups. Multiple signaling pathways that were closely associated with immune response, vasculogenesis, and smooth muscle contraction were indicated to participate in lncRNAs regulatory mechanism; of these, MAPK signaling pathway, which has been well studied for the treatment of many other cardiovascular diseases, was the core of this regulatory network. Our findings could help further understand the pathophysiology of MMD and provide new potential therapeutic targets.
Insights
Long noncoding RNA (lncRNA) expression differs significantly in moyamoya disease (MMD). These lncRNAs regulate pathways involved in inflammation and vascular disease, with the MAPK pathway being central, offering potential therapeutic targets.
Area of Science:
- Genomics
- Molecular Biology
- Vascular Biology
Background:
- Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive stenosis of the internal carotid arteries.
- The underlying pathophysiology of MMD is not fully understood, necessitating further investigation into molecular mechanisms.
- Long noncoding RNAs (lncRNAs) are emerging as critical regulators in various biological processes, including vascular development and disease.
Purpose of the Study:
- To investigate the differential expression patterns of lncRNAs in adult patients with MMD.
- To explore the potential roles of these dysregulated lncRNAs in the pathophysiology of MMD.
- To identify novel molecular targets for MMD treatment.
Main Methods:
- Peripheral blood samples were collected from MMD patients (n=15) and healthy controls (n=10).
- RNA extraction and microarray hybridization were performed to obtain lncRNA expression profiles.
- Bioinformatics analyses, including gene ontology and KEGG pathway enrichment, were used to identify target genes and regulatory pathways.
Main Results:
- A significant number of lncRNAs (3649) showed differential expression between MMD patients and controls, with 1494 upregulated and 2155 downregulated.
- Principal component analysis and hierarchical clustering clearly distinguished the MMD group from the control group.
- Enrichment analyses indicated that differentially expressed lncRNAs are involved in inflammation, vascular disease, and notably, the mitogen-activated protein kinase (MAPK) signaling pathway.
Conclusions:
- Distinct lncRNA expression profiles characterize MMD compared to healthy individuals.
- lncRNAs play a role in regulating pathways crucial for immune response, vasculogenesis, and smooth muscle contraction in MMD.
- The MAPK signaling pathway emerges as a core regulatory network in MMD pathophysiology, presenting a promising target for future therapeutic strategies.
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