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Published on: February 20, 2019
Role of MEG3 in Cellular Physiology of Atherosclerosis
Yu-Ting Wu1, Zhi-Jun Guo1, Jiang-Bin Li2
1Department of Geriatrics, Quanzhou First Hospital, Quanzhou, Fujian, China.
Objective:
To investigate the role of the lncRNA MEG3 (MEG3) in opposing the biochemical processes thought to be involved in the development of atherosclerosis (AS).
Methods:
Thirty patients with AS and thirty healthy control subjects were enrolled in this study. The expression of MEG3, miR-200b-3p and ABCA1 was analyzed by RT-qPCR in the individuals and the macrophages-derived foam cells. Lipid accumulation was detected by oil red O staining. Cholesterol efflux was measured by ELISA assay in the foam cells. Expression of miR-200b-3p was identified by sequencing. Targeting relationships were determined by dual luciferase assay between MEG3 and miR-200b-3p, miR-200b-3p and ABCA1.
Results:
In the patients with AS, MEG3 and ABCA1 expression were decreased and miR-200b-3p expression was upregulated. Foam cells transfected with an expression vector (pcDNA3.1) containing MEG3 (pcDNA3.1-MEG3) induced decrease of lipid accumulation and increase of cholesterol efflux compared to cells transfected with control plasmid alone. Foam cells transfected by pcDNA3.1-MEG3 also showed decreased miR-200b-3p and increased ABCA1 expression. Interestingly, co-expression of miR-200b-3p partially prevented these effects of MEG3 expression.
Conclusion:
Expression of MEG3 is downregulated in the patients with AS and foam cells. Overexpressed MEG3 may act as an anti-atherosclerotic factor by reducing lipid accumulation and accelerating cholesterol efflux through the miR-200b-3p/ABCA1 axis.
Insights
Long non-coding RNA MEG3 (MEG3) is downregulated in atherosclerosis (AS). Overexpressing MEG3 reduces lipid accumulation and enhances cholesterol efflux, suggesting it acts as an anti-atherosclerotic factor via the miR-200b-3p/ABCA1 pathway.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Genetics
Background:
- Atherosclerosis (AS) involves complex biochemical processes.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in disease pathogenesis.
Purpose of the Study:
- To investigate the role of lncRNA MEG3 in counteracting the biochemical mechanisms underlying atherosclerosis development.
- To elucidate the molecular pathway involving MEG3, miR-200b-3p, and ABCA1 in AS.
Main Methods:
- Expression analysis of MEG3, miR-200b-3p, and ABCA1 in AS patients and healthy controls using RT-qPCR.
- Assessment of lipid accumulation and cholesterol efflux in macrophage-derived foam cells.
- Dual luciferase assays to determine targeting relationships between MEG3, miR-200b-3p, and ABCA1.
Main Results:
- MEG3 and ABCA1 expression were decreased, while miR-200b-3p was upregulated in AS patients.
- Overexpression of MEG3 in foam cells reduced lipid accumulation and increased cholesterol efflux.
- MEG3 overexpression led to decreased miR-200b-3p and increased ABCA1 expression, with partial reversal by co-expressed miR-200b-3p.
Conclusions:
- MEG3 expression is reduced in atherosclerosis and foam cells.
- Upregulated MEG3 exhibits anti-atherosclerotic effects by modulating lipid accumulation and cholesterol efflux.
- The miR-200b-3p/ABCA1 axis is a key mediator of MEG3's protective function in AS.
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