IL-1ß promotes hypoxic vascular endothelial cell proliferation through the miR-24-3p/NKAP/NF-κB axis.
Biosci Rep
; 42(1)2022 01 28.
Article
em En
| MEDLINE
| ID: mdl-35005769
ABSTRACT
PURPOSE:
Our previous data indicated that miR-24-3p is involved in the regulation of vascular endothelial cell (EC) proliferation and migration/invasion. However, whether IL-1ß affects hypoxic HUVECs by miR-24-3p is still unclear. Therefore, the present study aimed to investigate the role and underlying mechanism of interleukin 1ß (IL-1ß) in hypoxic HUVECs.METHODS:
We assessed the mRNA expression levels of miR-24-3p, hypoxia-inducible factor-1α (HIF1A) and NF-κB-activating protein (NKAP) by quantitative real-time polymerase chain reaction (RT-qPCR). ELISA measured the expression level of IL-1ß. Cell counting kit-8 (CCK-8) assays evaluated the effect of miR-24-3p or si-NKAP+miR-24 on cell proliferation (with or without IL-1ß). 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-1ß). Luciferase reporter assays were used to identify the target of miR-24-3p.RESULTS:
We demonstrated that in acute myocardial infarction (AMI) patient blood samples, the expression of miR-24-3p is down-regulated, the expression of IL-1ß or NKAP is up-regulated, and IL-1ß or NKAP is negatively correlated with miR-24-3p. Furthermore, IL-1ß promotes hypoxic HUVECs proliferation by down-regulating miR-24-3p. In addition, IL-1ß 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 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-κB/pro-IL-1ß signaling pathway. However, IL-1ß 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-1ß in suppressing miR-24-3p up-regulation of the NKAP/NF-κB pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Células Endoteliais
/
Interleucina-1beta
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article