MicroRNA-3188 targets ETS-domain protein 4 and participates in RhoA/ROCK pathway to regulate the development of atherosclerosis.
Pharmazie
; 72(11): 687-693, 2017 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-29442044
ABSTRACT
We aimed to elucidate the roles and regulatory mechanism of miR-3188 in oxidized low-density lipoprotein (ox-LDL)-induced cell injury in THP-1 derived macrophages, thus providing a new insight for the treatment of atherosclerosis (AS). A total of 85 AS patients and 45 healthy controls were enrolled. The levels of miR-3188 and lipoprotein-associated phospholipase A2 (Lp-PLA2) in AS patients and healthy controls were detected. Then ox-LDL was used to treat human THP-1 derived macrophages. The effects of overexpression and suppression of miR-3188 on regulating ox-LDL-induced cell injury in THP-1 derived macrophages were investigated. Additionally, the potential target of miR-3188 was identified, which was verified by luciferase reporter assay. Besides, the relationship between miR-3188 and RhoA/ROCK pathway was explored. miR-3188 was downregulated in AS patients, while the levels of Lp-PLA2 in AS patients were increased. Ox-LDL significantly induced cell injury by decreasing cell viability, inducing cell apoptosis and increasing the production of inflammatory cytokines, including IL-1ß, IL-6, MCP-1 and TNF-α. In addition, miR-3188 was significantly downregulated after ox-LDL treatment. Overexpression of miR-3188 alleviated ox-LDL-induced cell injury, while inhibition of miR-3188 had opposite effects. ETS-domain protein 4 (ELK4) was a target of miR-3188. The effects of miR-3188 inhibition on ox-LDL-induced cell injury were markedly reversed by knockdown of ELK4. Besides, inhibition of miR-3188 enhanced ox-LDL-activated RhoA/ROCK pathway, while knockdown of ELK4 suppressed this pathway. Downregulation of miR-3188 may contribute to AS development via negatively regulating Lp-PLA2, targeting ELK4 and activating RhoA/ROCK pathway. miR-3188 may serve as a target for AS treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína rhoA de Ligação ao GTP
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MicroRNAs
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Aterosclerose
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Proteínas Elk-4 do Domínio ets
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Quinases Associadas a rho
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Pharmazie
Assunto da revista:
FARMACIA
Ano de publicação:
2017
Tipo de documento:
Article