Long Noncoding RNA OIP5-AS1 Contributes to the Progression of Atherosclerosis by Targeting miR-26a-5p Through the AKT/NF-κB Pathway.

Abstract

Atherosclerosis (AS) is a cardiovascular disease caused by multiple factors, leading to high mortality and morbidity in aged people. Some long noncoding RNAs have been reported to be associated with AS progression. However, the roles of OIP5-AS1 in AS development are still little known. In this study, the levels of OIP5-AS1 and miR-26a-5p in oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs) were determined by quantitative real-time polymerase chain reaction. Cell proliferation and apoptosis were evaluated by Cell Counting Kit-8 assay and flow cytometric analysis, respectively. The protein levels of proliferating cell nuclear antigen, B-cell lymphoma-2, cleaved caspase 3, inflammatory cytokines (IL-6 and IL-1β), protein kinase B (AKT), p-AKT, p65, p-p65, IκBα, and p-IκBα were detected by Western blot analysis. The targeting relationship between OIP5-AS1 and miR-26a-5p was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay. As a result, the expression of OIP5-AS1 was upregulated and miR-26a-5p was downregulated in ox-LDL-treated HUVECs. MiR-26a-5p was identified as a direct target of OIP5-AS1. OIP5-AS1 knockdown reversed the inhibitory effect on cell proliferation and the promotional effects on apoptosis and inflammation induced by ox-LDL treatment in HUVECs. Interestingly, the effects caused by OIP5-AS1 knockdown were further attenuated by miR-26a-5p inhibition. Furthermore, OIP5-AS1 knockdown blocked the AKT/NF-κB pathway by regulating miR-26a-5p expression. In conclusion, OIP5-AS1 knockdown promoted cell proliferation and suppressed apoptosis and inflammatory response in ox-LDL-treated HUVECs by targeting miR-26a-5p through blocking the AKT/NF-κB pathway, indicating a promising strategy for AS treatment.