TUG1 knockdown ameliorates atherosclerosis via up-regulating the expression of miR-133a target gene FGF1.
Cardiovasc Pathol
; 33: 6-15, 2018.
Article
em En
| MEDLINE
| ID: mdl-29268138
ABSTRACT
BACKGROUND:
Long non-coding RNAs (lncRNAs) have been revealed to participate in the pathological events associated with atherosclerosis. However, the exact role of lncRNA taurine-up-regulated gene 1 (TUG1) and its possible molecular mechanism in atherosclerosis remain unidentified.METHODS:
High-fat diet (HFD)-treated ApoE-/- mice were used as an in vivo model of atherosclerosis. Ox-LDL-induced macrophages and vascular smooth muscle cells (VSMCs) were employed as cell models of atherosclerosis. qRT-PCR was performed to detect the expression of TUG1 and miR-133a. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were analyzed by commercially available enzyme kits. Oil red O and hematoxylin and eosin (H&E) staining were conducted to examine atherosclerotic lesion. Luciferase reporter assay combined with RNA immunoprecipitation (RIP) was applied to confirm the interaction between TUG1, miR-133a and FGF1. Cell proliferation ability was determined by Cell Counting Kit-8 (CCK-8) assay and trypan blue dye exclusion test. Cell apoptosis was evaluated with TUNEL assay. Expression and production of inflammatory cytokines was measured with western blot and ELISA analysis.RESULTS:
TUG1 expression was up-regulated in HFD-treated ApoE-/- mice, as well as in ox-LDL-induced RAW264.7 and MOVAS cells. TUG1 knockdown inhibited hyperlipidemia, decreased inflammatory response, and attenuated atherosclerotic lesion in HFD-treated ApoE-/- mice. TUG1 could function as a molecular sponge of miR-133a to suppress its expression. TUG1 overexpression accelerated cell growth, improved inflammatory factor expression, and inhibited apoptosis in ox-LDL-stimulated RAW264.7 and MOVAS cells, while this effect was abated after transfection with miR-133 mimic. Moreover, fibroblast growth factor 1 (FGF1) was identified as a direct target of miR-133a. Restored expression of FGF1 overturned the effect of miR-133a on cell proliferation, inflammatory factor secretion and apoptosis in ox-LDL-treated RAW264.7 and MOVAS cells. Finally, TUG1 was revealed to up-regulate FGF1 expression by sponging miR-133a.CONCLUSION:
TUG1 knockdown ameliorates atherosclerosis by modulating FGF1 via miR-133a, raising the possibility of targeting TUG1 as an atheroprotective therapeutic strategy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aorta
/
Doenças da Aorta
/
Fator 1 de Crescimento de Fibroblastos
/
MicroRNAs
/
Aterosclerose
/
Técnicas de Silenciamento de Genes
/
Placa Aterosclerótica
/
RNA Longo não Codificante
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article