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KMID : 0381120210430080837
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Genes and Genomics
2021 Volume.43 No. 8 p.837 ~ p.846
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GAS5 regulates viability and apoptosis in TGF-β1-stimulated bronchial epithelial cells by regulating miR-217/HDAC4 axis
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Zhao Sihui
Ning Yunfang
Qin Na
Ping Nan
Yu Yong
Yin Guoyan
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Abstract
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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-β1 (TGF-β1) 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-β1-induced injury of airway epithelial. However, the mechanism underlying TGF-β1-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-β1-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-β1, GAS5, HDAC4 were up-regulated, while miR-217 was down-regulated in bronchial mucosal tissues of asthmatic children and TGF-β1-treated BEAS-2B cells. TGF-β1 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-β1-induced BEAS-2B cells. GAS5 knockdown induced cell viability and hampered cell apoptosis in TGF-β1-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-β1-induced bronchial epithelial cells injury, thus contributing to asthma.
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KEYWORD
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Asthma, TGF-β1, GAS5, MiR-217, HDAC4
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