Dataset Information

Long noncoding RNA OIP5-AS1 accelerates the ox-LDL mediated vascular endothelial cells apoptosis through targeting GSK-3? via recruiting EZH2.

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-3? expression through recruiting EZH2, a critical element of the Polycomb Repressive Complex 2 (PRC2) complex that directly bind with the GSK-3? promoter region. Rescue experiments validated that GSK-3? 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-3? via recruiting EZH2, providing potential therapeutic strategies for atherosclerosis.

SUBMITTER: Wang M

PROVIDER: S-EPMC6456540 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Long noncoding RNA OIP5-AS1 accelerates the ox-LDL mediated vascular endothelial cells apoptosis through targeting GSK-3β via recruiting EZH2.

Wang Minghui M Liu Yujie Y Li Chao C Zhang Ying Y Zhou Xiujun X Lu Chengzhi C

American journal of translational research 20190315 3

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 silenc ...[more]

PMID: 30972206

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Project description:Background: Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of atherosclerosis. LncRNA OIP5 antisense RNA 1 (OIP5-AS1) has been found to be associated with the development of atherosclerosis. In this study, we further investigated the molecular basis of OIP5-AS1 in atherosclerosis pathogenesis. Methods: Oxidative low-density lipoprotein (ox-LDL) was used to treat human umbilical vein endothelial cells (HUVECs). The levels of OIP5-AS1, miR-135a-5p, and Krüppel-like factor 5 (KLF5) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability, migration, and apoptosis were evaluated using the Cell Counting Kit-8 (CCK-8), Transwell, and flow cytometry, respectively. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA) were determined with enzyme-linked immunosorbent assay (ELISA). Targeted interactions among OIP5-AS1, miR-135a-5p, and KLF5 were confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Animal studies were performed to assess the role of OIP5-AS1 in atherosclerosis progression in vivo. Results: Our data showed the significant upregulation of OIP5-AS1 in atherosclerosis serum and ox-LDL-stimulated HUVECs. The silencing of OIP5-AS1 protected against ox-LDL-triggered cytotoxicity in HUVECs and diminished lipids secretion in ApoE-/- mice. Moreover, OIP5-AS1 functioned as a molecular sponge of miR-135a-5p, and miR-135a-5p was a functional mediator of OIP5-AS1 in regulating ox-LDL-induced HUVEC injury. KLF5 was a direct target of miR-135a-5p, and the increased expression of miR-135a-5p alleviated ox-LDL-induced cytotoxicity by downregulating KLF5. Furthermore, OIP5-AS1 influenced KLF5 expression through sponging miR-135a-5p. Conclusion: The current work identified that the silencing of OIP5-AS1 protected against ox-LDL-triggered cytotoxicity in HUVECs at least in part by influencing KLF5 expression via acting as a miR-135a-5p sponge.

Dataset Information

Long noncoding RNA OIP5-AS1 accelerates the ox-LDL mediated vascular endothelial cells apoptosis through targeting GSK-3? via recruiting EZH2.

Publications

Long noncoding RNA OIP5-AS1 accelerates the ox-LDL mediated vascular endothelial cells apoptosis through targeting GSK-3β via recruiting EZH2.

Similar Datasets

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