CircIRAK1 aggravates ox-LDL-induced endothelial cell injury in atherosclerosis via TRIM14 upregulation by binding to miR-330-5p.

BACKGROUND

Atherosclerosis (AS) is a common inflammatory cardiovascular disease, and circular RNAs (circRNAs) are associated with the pathogenesis of AS. CircRNA Interleukin (IL)-1 receptor-associated kinase 1 (circIRAK1, hsa_circ_0091822) was upregulated in AS. The aims of this study were to ascertain the function and mechanism of circIRAK1 in AS.

METHODS

Human Umbilical Vein Endothelial Cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL). RNA expression was detected by reverse transcription-quantitative polymerase chain reaction assay. Cell viability was examined using Cell Counting Kit-8 assay. Tube formation ability was measured by tube formation assay. Cell apoptosis was assessed using flow cytometry. Western blot was used for protein detection. Inflammatory reaction was evaluated via Enzyme-linked immunosorbent assay. Oxidative injury was analyzed by commercial kits. Target binding was determined through dual-luciferase reporter assay, RNA immunoprecipitation assay and pull-down assay.

RESULTS

The expression of circIRAK1 was upregulated in AS serums and ox-LDL-treated HUVECs. Silencing circIRAK1 enhanced cell viability and angiogenesis while suppressed cell apoptosis, inflammatory response and oxidative stress in ox-LDL-stimulated HUVECs. CircIRAK1 served as a molecular sponge for miR-330-5p. CircIRAK1 regulated ox-LDL-mediated cell injury by absorbing miR-330-5p. In addition, miR-330-5p prevented endothelial cell dysfunction caused by ox-LDL via targeting tripartite motif containing 14 (TRIM14). TRIM14 expression was upregulated by circIRAK1 through sponging miR-330-5p.

CONCLUSION

These results suggested that circIRAK1 upregulated TRIM14 by interacting with miR-330-5p, consequently contributing to ox-LDL-induced endothelial cell injury in AS.