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Author Spotlight: A Computational Pipeline for Analyzing Chimeric Noncoding RNA-Target RNA Interactions in High-Throughput Sequencing Data
Published on: December 1, 2023
Long noncoding RNA OIP5-AS1 accelerates the ox-LDL mediated vascular endothelial cells apoptosis through targeting
Minghui Wang1,2, Yujie Liu2, Chao Li2
1Tianjin Medical University Tianjin 300070, China.
Abstract:
An increasing amount of research is demonstrating the role of long noncoding RNAs (lncRNAs) in human cardiovascular disease, and in particular, atherosclerosis. To date, the mechanism through which lncRNA OIP5-AS1 regulates the oxidative low-density lipoprotein (ox-LDL)-mediated endothelial cell apoptosis is still unclear. Results from this study found that lncRNA OIP5-AS1 was significantly over-expressed in the human umbilical vein endothelial cells (HUVECs) administered with ox-LDL. The silencing of OIP5-AS1 inhibited apoptosis and promoted proliferation via inducing G0/G1 cycle arrest. Chromatin immunoprecipitate (ChIP) revealed that lncRNA OIP5-AS1 reduced GSK-3β expression through recruiting EZH2, a critical element of the Polycomb Repressive Complex 2 (PRC2) complex that directly bind with the GSK-3β promoter region. Rescue experiments validated that GSK-3β could eliminate the effect of OIP5-AS1 on HUVECs. Overall, these findings suggest that lncRNA OIP5-AS1 accelerates ox-LDL mediated vascular endothelial cell apoptosis through targeting GSK-3β via recruiting EZH2, providing potential therapeutic strategies for atherosclerosis.
Insights
Long noncoding RNA OIP5-AS1 accelerates atherosclerosis by promoting endothelial cell apoptosis. It targets GSK-3β via EZH2, offering potential therapeutic strategies for cardiovascular disease.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- RNA Biology
Background:
- Long noncoding RNAs (lncRNAs) are increasingly implicated in cardiovascular diseases like atherosclerosis.
- The precise mechanism of lncRNA OIP5-AS1 in oxidative low-density lipoprotein (ox-LDL)-induced endothelial cell apoptosis remains largely unknown.
Purpose of the Study:
- To elucidate the role and mechanism of lncRNA OIP5-AS1 in ox-LDL-mediated endothelial cell apoptosis.
- To investigate the interaction between OIP5-AS1, EZH2, and GSK-3β in the context of atherosclerosis.
Main Methods:
- Quantitative analysis of OIP5-AS1 expression in ox-LDL treated human umbilical vein endothelial cells (HUVECs).
- OIP5-AS1 silencing experiments to assess effects on apoptosis and cell cycle.
- Chromatin immunoprecipitation (ChIP) assays to determine the recruitment of EZH2 to the GSK-3β promoter.
- Rescue experiments to validate the role of GSK-3β.
Main Results:
- OIP5-AS1 was significantly over-expressed in ox-LDL treated HUVECs.
- Silencing OIP5-AS1 inhibited apoptosis and promoted proliferation by inducing G0/G1 cell cycle arrest.
- OIP5-AS1 recruits EZH2 to the GSK-3β promoter, leading to reduced GSK-3β expression.
- GSK-3β was found to counteract the effects of OIP5-AS1.
Conclusions:
- lncRNA OIP5-AS1 accelerates ox-LDL-mediated vascular endothelial cell apoptosis by targeting GSK-3β through EZH2 recruitment.
- These findings highlight OIP5-AS1 as a potential therapeutic target for atherosclerosis.
- The OIP5-AS1/EZH2/GSK-3β axis represents a novel pathway in endothelial cell apoptosis regulation.
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