Mechanism of LncRNA DDX11-AS1 targeting miR-627-3p in regulating proliferation and apoptosis of vascular endothelial cells induced by oxidized low-density lipoprotein

  Objective  To investigate the roles of long non-coding RNA (LncRNA) DDX11 antisense RNA1 (DDX11-AS1) on proliferation and apoptosis of vascular endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) and its mechanism.

  Methods  Human umbilical vein endothelial cells (HUVEC) was treated with 50 μg/mL ox-LDL to construct atherosclerosis cell model. Cell proliferation and apoptosis were detected by cell counting kit (CCK-8) and flow cytometry, the expression levels of DDX11-AS1 and miR-627-3p were measured by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), and the phosphorylation level of nuclear transcription factor P65 subunit (p65) and nuclear transcription factor inhibitory protein α (IкBα) were detect by western blot. The DDX11-AS1 overexpressed plasmid and miR-627-3p inhibitors were transfected into HUVEC respectively, and the effects of up-regulation of DDX11-AS1 or down-regulation of miR-627-3p on the proliferation and apoptosis of HUVEC treated with ox-LDL were detected by the above methods. The interaction between DDX11-AS1 and miR-627-3p was determined by luciferase reporter gene method and RT-qPCR.

  Results  The expression of miR-627-3p, apoptosis rate and phosphorylation level of P65 and IкBα were significantly increased, the expression of DDX11-AS1 and cell survival rate were significantly reduced in ox-LDL-treated HUVEC (P < 0.05). After up-regulating the expression of DDX11-AS1, the survival rate of HUVEC treated with ox-LDL was significantly increased, the apoptosis rate and the phosphorylation levels of p65 and IкBα were significantly reduced (P < 0.05). After down-regulating the expression of miR-627-3p, the survival rate of HUVEC treated with ox-LDL was significantly increased, the apoptosis rate was significantly decreased (P < 0.05). The miR-627-3p was the target gene of DDX11-AS1, and DDX11-AS1 negatively regulated miR-627-3p expression. Up-regulation of miR-627-3p could reverse the effects of DDX11-AS1 up-regulation on the survival, apoptosis, and phosphorylation of p65 and IкBα in HUVEC treated with ox-LDL (P < 0.05).

  Conclusion  LncRNA DDX11-AS1 can inhibit ox-LDL-induced vascular endothelial cell apoptosis and promote cell proliferation by targeting miR-627-3p, thereby reducing ox-LDL-induced cell damage.