LncRNA FOXC2-AS1 regulated proliferation and apoptosis of vascular smooth muscle cell through targeting miR-1253/FOXF1 axis in atherosclerosis.
Eur Rev Med Pharmacol Sci
; 24(6): 3302-3314, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-32271448
ABSTRACT
OBJECTIVE:
Atherosclerosis (AS) is the most dangerous factor for human death, which is responsible for coronary heart disease. Growing evidence has showed that long non-coding RNAs (lncRNAs) are involved in the development of AS. In this study, we mainly aimed at investigating the roles of FOXC2-AS1 in AS patients. PATIENTS ANDMETHODS:
RT-PCR was performed to detect the expressions of FOXC2-AS1 and miR-1253 in serum samples of AS patients (n=35) and healthy volunteer (n=35). The correlation between FOXC2-AS1 and miR-1253 was further analyzed. Human vascular smooth muscle cells (VSMCs) were respectively treated with ox-LDL, IL-6, CRP, TNF-α and IL-8 to explore the affecting factors. P-FOXC2-AS1 was constructed and transfected into VSMCs. Cell proliferation abilities were measured by CCK-8 assay. Cell apoptotic rates were measured by ï¬ow cytometry (FACS) analysis. Western blot (WB) was performed to detect protein levels of FOXF1, Bcl-2, Bax and Cleaved Caspase3. Finally, luciferase gene reporter assay was performed to prove the relationships between FOXC2-AS1 and miR-1253, miR-1253 and FOXF1.RESULTS:
We found that FOXC2-AS1 was significantly upregulated in AS patients, which could be induced by ox-LDL and IL-6 in VSMCs. MiR-1253 was decreased in AS patients, which was negatively correlated with FOXC2-AS1. Furthermore, FOXC2-AS1 overexpression promoted proliferation and inhibited apoptosis in VSMCs. Luciferase gene reporter assay showed that FOXC2-AS1 could bind to miR-1253 in VSMCs and 293 cells. Moreover, miR-1253 overexpression inhibited proliferation and promoted apoptosis of VSMCs. Luciferase reporter assay proved that miR-1253 could target at FOXF1 in VSMCs and 293 cells, which was reported to be associated with cell proliferation and apoptosis in some cancers. Additionally, miR-1253 mimic or GSK343, a FOXF1 inhibitor, was respectively transfected into VSMCs with p-FOXC2-AS1. Results showed that the promoted cell proliferation and inhibited cell apoptosis were reversed as well, confirming that FOXC2-AS1 promoted cell proliferation and inhibited apoptosis via miR-1253/FOXF1 signaling axis in AS patients.CONCLUSIONS:
According to the results, we found that FOXC2-AS1 was upregulated in AS patients; furthermore, FOXC2-AS1 overexpression promoted cell proliferation and inhibited cell apoptosis via targeting miR-1253/FOXF1 signaling axis. Our results elucidated a potential mechanism underlying the role of FOXC2-AS1, which might be used as a promising marker and a potential target for AS patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
6_cardiovascular_diseases
Assunto principal:
MicroRNAs
/
Aterosclerose
/
Fatores de Transcrição Forkhead
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Eur Rev Med Pharmacol Sci
Assunto da revista:
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China