IL-1β promotes hypoxic vascular endothelial cell proliferation through the miR-24-3p/NKAP/NF-kB axis

Purpose: Our previous data indicated that miR‑24-3p is involved in the regulation of vascular endothelial cell proliferation and migration/invasion. However, whether IL-1β affects hypoxic HUVECs by miR-24-3p is still unclear. Therefore, the present study aimed to investigate the role and underlying mechanism of IL-1β in hypoxic HUVECs. Methods: We assessed the mRNA expression levels of miR-24-3p, HIF1A and NKAP by RT-qPCR. ELISA measured the expression level of IL-1β. CCK-8 assays evaluated the effect of miR-24-3p or si-NKAP+miR-24 on cell proliferation (with or without IL-1β). Transwell migration and invasion assays were used to examine the effects of miR-24-3p or si-NKAP+miR-24-3p on cell migration and invasion (with or without IL-1β). Luciferase reporter assays were used to identify the target of miR-24-3p. Results: We demonstrated that in AMI patient blood samples, the expression of miR-24-3p is downregulated, the expression of IL-1β or NKAP is upregulated, and IL-1β or NKAP is negatively correlated with miR-24-3p. Furthermore, IL-1β promotes hypoxic HUVECs proliferation by downregulating miR-24-3p. In addition, IL-1β also significantly promotes the migration and invasion of hypoxic HUVECs; overexpression of miR-24-3p can partially rescue hypoxic HUVECs migration and invasion. Furthermore, we discovered that NF-kappa-B-activating protein (NKAP) is a novel target of miR-24-3p in hypoxic HUVECs. Moreover, both the overexpression of miR-24-3p and the suppression of NKAP can inhibit the NF-kB/pro-IL-1β signaling pathway. However, IL‑1β mediates suppression of miR-24-3p activity, leading to activation of the NKAP/NF‑κB pathway. In conclusion, our results reveal a new function of IL‑1β in suppressing miR-24-3p upregulation of the NKAP/NF-kB pathway.