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.

Long non-coding RNA OIP5-AS1 aggravates acute lung injury through promoting inflammation and cell apoptosis via regulating miR-26a-5p/TLR4 axis

“…In arheumatoid arthritis, OIP5-AS1 was proposed to inhibit in ammation response via blocking TLR3-NF-κB pathway . In atherosclerosis, OIP5-AS1 was con rmed to facilitate cell apoptosis and in ammation by activating AKT/NF-κB pathway (Ren et al, 2020). In current study, we identi ed that miR-26a-5p negatively regulated the expression of OIP5-AS1.…”

“…Recently, lncRNA OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been reported to involve in diverse pathogeneses including tumors (Chen et al, 2019;Ma et al, 2020), myocardial ischaemia/reperfusion (MI/R) injury (Niu et al, 2020), and osteoarthritis (Zhi et al, 2020). Moreover, OIP5-AS1 was proven to regulate cell injury and in ammatory response in atherosclerosis and rheumatoid arthritis Ren et al, 2020). However, the role of OIP5-AS1 remained to be studied in ALI.…”

The Integrative Analysis of Competitive Endogenous RNA Regulatory Networks in Coronary Artery Disease

“…Some studies have shown that OIP5-AS1 is related to the pathophysiological process of atherosclerosis. A previous study demonstrated that OIP5-AS1 contributed to the progression of atherosclerosis by targeting miR-26a-5p, and OIP5-AS1 knockdown could promote cell proliferation and reduce apoptosis and inflammatory response ( 12 ). A recent integrated analysis identified six key lncRNAs, including OIP5-AS1, whose expression pattern was highly correlated with the disease stage of atherogenesis ( 13 ).…”

LncRNA OIP5-AS1 targets miR-25-3p to accelerate intervertebral disc degeneration

“…Through searching on NCBI website, we discovered that lncRNA OIP5-AS1 is a promotive molecule in different diseases. During the process of atherosclerosis, lncRNA OIP5-AS1 targets miR-26a-5p to modulate AKT/NF-κB pathway and exerts promotion effect [20]. LncRNA OIP5-AS1 indicates dismal prognosis and mediates cell proliferation in bladder cancer through OIP5 [21].…”