Long non-coding RNA NEAT1 regulates endothelial functions in subclinical hypothyroidism through miR-126/TRAF7 pathway.
Hum Cell
; 34(3): 825-835, 2021 May.
Article
em En
| MEDLINE
| ID: mdl-33677813
ABSTRACT
Subclinical hypothyroidism (SCH) is associated with increased risks of endothelial dysfunction and atherosclerosis, but the mechanisms remain unclear. In our previous study, microRNA-126-3p was downregulated in SCH, but the role and regulatory mechanism of miR-126 in SCH has not been investigated. A SCH mouse model was established by feeding mice methimazole. Both primary endothelial cells (ECs) and HUVECs were cultured. The expression levels of key molecules were detected via quantitative RT-PCR, western blotting, and immunofluorescence. Wire myography was used to analyze the changes in vascular tones. A dual-luciferase assay was used to investigate the relationship between lncRNAs, microRNAs and target genes. In detail, it was shown that the expression levels of miR-126-3p were significantly decreased in both the SCH vasculature and HUVECs. MiR-126 supplementation suppressed HUVEC apoptosis and improved vascular function. Moreover, miR-126 could bind to the 3'-untranslated region of TRAF7, thus, regulating the C-FLIP pathway and endothelial apoptosis. Furthermore, lncRNA NEAT1 was upregulated upon TSH treatment and could function as a ceRNA and bind to miR-126, thus, modulating its expression level and vascular function. Finally, the NEAT1/miR-126/TRAF7 axis functions in response to TSH and regulates endothelial functions in SCH in vitro and in vivo. In conclusion, dysregulation of the NEAT1/miR-126/TRAF7 axis is responsible for impaired endothelial functions in SCH. Targeting this axis might become a promising treatment strategy or improving endothelial functions in SCH.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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MicroRNAs
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Células Endoteliais
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Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral
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RNA Longo não Codificante
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Hipotireoidismo
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Hum Cell
Ano de publicação:
2021
Tipo de documento:
Article