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Published on: June 15, 2018
Circular RNA circ_0026218 Suppressed Atherosclerosis Progression via miR-338-3p/SIRT6 Axis
Liang Yang1, Wei Chen1, Bin Li1
1Heart Center, Guilin People's Hospital, Guilin, 541002 Guangxi, China.
Insights
Circular RNA 0026218 (circ_0026218) protects against atherosclerosis by upregulating SIRT6 via sponging microRNA-338-3p. This mechanism inhibits oxidized low-density lipoprotein-induced injury in human umbilical vein endothelial cells, highlighting circ_0026218
Area of Science:
- Molecular Biology
- Cardiovascular Research
- RNA Biology
Background:
- Circular RNAs (circRNAs) play a role in atherosclerosis (AS) pathogenesis.
- The specific function of circRNA 0026218 (circ_0026218) in AS is not well understood.
- Investigating circ_0026218's role in vascular endothelial cell injury is crucial for understanding AS.
Purpose of the Study:
- To elucidate the function and mechanism of circ_0026218 in AS.
- To determine the effect of circ_0026218 on oxidized low-density lipoprotein (ox-LDL)-induced injury in human umbilical vein endothelial cells (HUVECs).
- To explore the relationship between circ_0026218, microRNA-338-3p (miR-338-3p), and silent information regulator 6 (SIRT6).
Main Methods:
- Differential expression screening of circRNAs in AS using microarray analysis.
- Establishment of an ox-LDL-induced HUVEC injury model.
- Assessment of cell viability, inflammatory response, oxidative stress, and apoptosis.
- Investigation of molecular interactions using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.
- Validation of protein expression changes via Western blot.
Main Results:
- circ_0026218 expression was significantly decreased in ox-LDL-treated HUVECs.
- Overexpression of circ_0026218 enhanced HUVEC viability and attenuated inflammatory response, oxidative stress, and apoptosis.
- circ_0026218 directly targets miR-338-3p, acting as a molecular sponge.
- circ_0026218 positively regulates SIRT6 expression by inhibiting miR-338-3p.
- Inhibition of miR-338-3p reversed the protective effects of circ_0026218.
Conclusions:
- circ_0026218 protects HUVECs from ox-LDL-induced injury by upregulating SIRT6 expression through sponging miR-338-3p.
- circ_0026218 is implicated in the pathogenesis of atherosclerosis.
- circ_0026218 represents a potential therapeutic target for AS.
Background:
Multiple circular RNAs (circRNAs) are implicated in atherosclerosis (AS) pathogenesis. In fact, how circRNA 0026218 (circ_0026218) functions in AS remains unknown, and thus the functions and mechanisms of circ_0026218 in the injury of vascular endothelial cells are to be investigated.
Methods:
Microarray analysis was employed to screen out differentially expressed circRNAs in AS. A cell model was mimicked by treating Human umbilical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (ox-LDL). circ_0026218, microRNA-338-3p (miR-338-3p) and silent information regulator 6 (SIRT6) expressions in HUVECs with ox-LDL treatment were probed by qRT-PCR. The cell proliferative capabilities were exposed by CCK-8 assay. The contents of interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α) were measured by ELISA. Oxidative stress kits were utilized to detect the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA). Flow cytometry was adopted to analyze the level of apoptosis of HUVECs. Dual-luciferase reporter gene assay and RIP assay were leveraged to expose the interplay between miR-338-3p and circ_0026218 or SIRT6 3'-UTR, respectively. In addition, the impacts of circ_0026216 and miR-338-3p on SIRT6 protein expressions were subjected to Western blot.
Results:
circ_0026218 was greatly depleted in ox-LDL-stimulated HUVECs. circ_0026218 overexpression promoted viability of HUVECs in vitro and inhibited inflammatory response, oxidative stress, and apoptosis. circ_0026218 could adsorb miR-338-3p and positively modulated SIRT6 expressions via sponging miR-338-3p. Upregulation of this miRNA reversed the influence of circ_0026218 overexpression on ox-LDL-caused injury and apoptosis of HUVECs.
Conclusion:
Collectively, circ_0026218 upregulates SIRT6 expression through decoying miR-338-3p, thereby inhibiting ox-LDL-initiated injury of HUVECs. circ_0026218 is involved in the pathogenesis of AS.
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