Circ-OSBPL2 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-193a-5p/BRD4 Axis
Caifen Zheng,1 Yongping Zhang,2 Yingchun Zhao,3 Yuanfang Duan,1 Qianghua Mu,1 Xinying Wang1 1Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 2Blood Purifying Center, The First People&rs...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2021-04-01
|
Series: | International Journal of COPD |
Subjects: | |
Online Access: | https://www.dovepress.com/circ-osbpl2-contributes-to-smoke-related-chronic-obstructive-pulmonary-peer-reviewed-article-COPD |
id |
doaj-a047f9a3b52b4a22bd9f8755c7eb432f |
---|---|
record_format |
Article |
spelling |
doaj-a047f9a3b52b4a22bd9f8755c7eb432f2021-04-08T20:41:21ZengDove Medical PressInternational Journal of COPD1178-20052021-04-01Volume 1691993163686Circ-OSBPL2 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-193a-5p/BRD4 AxisZheng CZhang YZhao YDuan YMu QWang XCaifen Zheng,1 Yongping Zhang,2 Yingchun Zhao,3 Yuanfang Duan,1 Qianghua Mu,1 Xinying Wang1 1Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 2Blood Purifying Center, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 3Department of Cardiovascular Medicine, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of ChinaCorrespondence: Yingchun ZhaoDepartment of Cardiovascular Medicine, The First People’s Hospital of Lianyungang, No. 6 East Zhenhua Road, Haizhou, Lianyungang, Jiangsu, 222061, People’s Republic of ChinaTel +86-0518-85767023Email zyc6469@126.comBackground: Circular RNAs (circRNAs) have been identified to play roles in the respiratory diseases. Here, this study aimed to elucidate the function of circRNA oxysterol binding protein like 2 (circOSBPL2) in the development of smoke-related chronic obstructive pulmonary diseases (COPD).Methods: The expression of circ-OSBPL2, microRNA (miR)-193a-5p, and bromodomain-containing protein 4 (BRD4) was detected using qRT-PCR and Western blot assays. Cigarette smoke extract (CSE)-induced human bronchial epithelial cells (HBECs) was applied to mimic smoke-related COPD in vitro. Flow cytometric analysis of cell apoptosis and ELISA analysis of interleukins (IL)-6, IL-8, tumor necrosis factor-α (TNF-α) levels were performed. The malondialdehyde (MDA) and superoxide dismutase (SOD) production levels were analyzed according to the kit instructions. The binding interaction between miR-193a-5p and circ-OSBPL2 or BRD4 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assays.Results: Circ-OSBPL2 was highly expressed in lung tissues of smokers without or with COPD, particularly in smokers with COPD. Also, the expression of circ-OSBPL2 was dose and time-dependently elevated in CSE-induced HBECs. Circ-OSBPL2 down-regulation in HBECs attenuated CSE-evoked cell proliferation arrest, and cell apoptosis, inflammation and oxidative stress promotion. Mechanistically, circ-OSBPL2 served as a sponge for miR-193a-5p, and miR-193a-5p inhibition reversed the effects of circ-OSBPL2 knockdown on CSE-mediated HBECs. Besides that, miR-193a-5p directly targeted BRD4, and miR-193a-5p re-expression in HBECs abolished CSE-induced HBEC injury, which was reverted by BRD4 up-regulation. Additionally, we also found circ-OSBPL2 could indirectly regulate BRD4 via miR-193a-5p.Conclusion: Circ-OSBPL2 contributed to the apoptosis, inflammation, and oxidative stress of HBECs in smoke-related COPD by miR-193a-5p/BRD4 axis, suggesting a novel insight on the pathogenesis of COPD and a potential therapeutic strategy for future clinic intervention in COPD.Keywords: circ-OSBPL2, miR-193a-5p, BRD4, COPDhttps://www.dovepress.com/circ-osbpl2-contributes-to-smoke-related-chronic-obstructive-pulmonary-peer-reviewed-article-COPDcirc-osbpl2mir-193a-5pbrd4copd |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zheng C Zhang Y Zhao Y Duan Y Mu Q Wang X |
spellingShingle |
Zheng C Zhang Y Zhao Y Duan Y Mu Q Wang X Circ-OSBPL2 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-193a-5p/BRD4 Axis International Journal of COPD circ-osbpl2 mir-193a-5p brd4 copd |
author_facet |
Zheng C Zhang Y Zhao Y Duan Y Mu Q Wang X |
author_sort |
Zheng C |
title |
Circ-OSBPL2 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-193a-5p/BRD4 Axis |
title_short |
Circ-OSBPL2 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-193a-5p/BRD4 Axis |
title_full |
Circ-OSBPL2 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-193a-5p/BRD4 Axis |
title_fullStr |
Circ-OSBPL2 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-193a-5p/BRD4 Axis |
title_full_unstemmed |
Circ-OSBPL2 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-193a-5p/BRD4 Axis |
title_sort |
circ-osbpl2 contributes to smoke-related chronic obstructive pulmonary disease by targeting mir-193a-5p/brd4 axis |
publisher |
Dove Medical Press |
series |
International Journal of COPD |
issn |
1178-2005 |
publishDate |
2021-04-01 |
description |
Caifen Zheng,1 Yongping Zhang,2 Yingchun Zhao,3 Yuanfang Duan,1 Qianghua Mu,1 Xinying Wang1 1Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 2Blood Purifying Center, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 3Department of Cardiovascular Medicine, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of ChinaCorrespondence: Yingchun ZhaoDepartment of Cardiovascular Medicine, The First People’s Hospital of Lianyungang, No. 6 East Zhenhua Road, Haizhou, Lianyungang, Jiangsu, 222061, People’s Republic of ChinaTel +86-0518-85767023Email zyc6469@126.comBackground: Circular RNAs (circRNAs) have been identified to play roles in the respiratory diseases. Here, this study aimed to elucidate the function of circRNA oxysterol binding protein like 2 (circOSBPL2) in the development of smoke-related chronic obstructive pulmonary diseases (COPD).Methods: The expression of circ-OSBPL2, microRNA (miR)-193a-5p, and bromodomain-containing protein 4 (BRD4) was detected using qRT-PCR and Western blot assays. Cigarette smoke extract (CSE)-induced human bronchial epithelial cells (HBECs) was applied to mimic smoke-related COPD in vitro. Flow cytometric analysis of cell apoptosis and ELISA analysis of interleukins (IL)-6, IL-8, tumor necrosis factor-α (TNF-α) levels were performed. The malondialdehyde (MDA) and superoxide dismutase (SOD) production levels were analyzed according to the kit instructions. The binding interaction between miR-193a-5p and circ-OSBPL2 or BRD4 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assays.Results: Circ-OSBPL2 was highly expressed in lung tissues of smokers without or with COPD, particularly in smokers with COPD. Also, the expression of circ-OSBPL2 was dose and time-dependently elevated in CSE-induced HBECs. Circ-OSBPL2 down-regulation in HBECs attenuated CSE-evoked cell proliferation arrest, and cell apoptosis, inflammation and oxidative stress promotion. Mechanistically, circ-OSBPL2 served as a sponge for miR-193a-5p, and miR-193a-5p inhibition reversed the effects of circ-OSBPL2 knockdown on CSE-mediated HBECs. Besides that, miR-193a-5p directly targeted BRD4, and miR-193a-5p re-expression in HBECs abolished CSE-induced HBEC injury, which was reverted by BRD4 up-regulation. Additionally, we also found circ-OSBPL2 could indirectly regulate BRD4 via miR-193a-5p.Conclusion: Circ-OSBPL2 contributed to the apoptosis, inflammation, and oxidative stress of HBECs in smoke-related COPD by miR-193a-5p/BRD4 axis, suggesting a novel insight on the pathogenesis of COPD and a potential therapeutic strategy for future clinic intervention in COPD.Keywords: circ-OSBPL2, miR-193a-5p, BRD4, COPD |
topic |
circ-osbpl2 mir-193a-5p brd4 copd |
url |
https://www.dovepress.com/circ-osbpl2-contributes-to-smoke-related-chronic-obstructive-pulmonary-peer-reviewed-article-COPD |
work_keys_str_mv |
AT zhengc circosbpl2contributestosmokerelatedchronicobstructivepulmonarydiseasebytargetingmir193a5pbrd4axis AT zhangy circosbpl2contributestosmokerelatedchronicobstructivepulmonarydiseasebytargetingmir193a5pbrd4axis AT zhaoy circosbpl2contributestosmokerelatedchronicobstructivepulmonarydiseasebytargetingmir193a5pbrd4axis AT duany circosbpl2contributestosmokerelatedchronicobstructivepulmonarydiseasebytargetingmir193a5pbrd4axis AT muq circosbpl2contributestosmokerelatedchronicobstructivepulmonarydiseasebytargetingmir193a5pbrd4axis AT wangx circosbpl2contributestosmokerelatedchronicobstructivepulmonarydiseasebytargetingmir193a5pbrd4axis |
_version_ |
1721533817508855808 |