GAS5 regulates viability and apoptosis in TGF-ß1-stimulated bronchial epithelial cells by regulating miR-217/HDAC4 axis.
Genes Genomics
; 43(8): 837-846, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-33864612
ABSTRACT
BACKGROUND:
Asthma is a serious respiratory disease that affects the physical and mental health of children. Airway epithelial apoptosis concomitantly mediated by transforming growth factor-ß1 (TGF-ß1) is a crucial component of asthma pathogenesis. LncRNA growth Arrest Specific 5 (GAS5), microRNA-217 (miR-217) and Histone deacetylase 4 (HDAC4) shown a close relationship with TGF-ß1-induced injury of airway epithelial. However, the mechanism underlying TGF-ß1-induced injury of airway epithelial in asthma still needs to be investigated.OBJECTIVE:
We aimed to investigate the effect and underlying mechanism of GAS5/miR-217/HDAC4 axis in TGF-ß1-stimulated bronchial epithelial cells.METHODS:
The levels of were detected by quantitative real-time polymerase chain reaction (RT-qPCR). All protein levels were determined by western blot. Cell viability and apoptosis rate were assessed by Methyl thiazolyl tetrazolium (MTT) and Flow cytometry, respectively. The targeting relationship between miR-217 and GAS5 or HDAC4 was examined with dual-luciferase reporter assay.RESULTS:
TGF-ß1, GAS5, HDAC4 were up-regulated, while miR-217 was down-regulated in bronchial mucosal tissues of asthmatic children and TGF-ß1-treated BEAS-2B cells. TGF-ß1 could reduce cell viability and induce apoptosis, while these effects could be reversed by downregulation of GAS5 or HDAC4. Mechanically, GAS5 acted as a sponge for miR-217 to regulate the expression of HDAC4. Furthermore, overexpression of HDAC4 rescued the effects of GAS5 knockdown on viability and apoptosis of TGF-ß1-induced BEAS-2B cells. GAS5 knockdown induced cell viability and hampered cell apoptosis in TGF-ß1-stimulated BEAS-2B cells by regulating the miR-217/HDAC4 axis.CONCLUSIONS:
The lncRNA GAS5/miR-217/HDAC4 axis played an important role in regulating TGF-ß1-induced bronchial epithelial cells injury, thus contributing to asthma.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Brônquios
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MicroRNAs
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Fator de Crescimento Transformador beta1
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RNA Longo não Codificante
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Histona Desacetilases
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article