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Circ-OSBPL2 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-193a-5p/BRD4 Axis

Authors Zheng C, Zhang Y, Zhao Y, Duan Y, Mu Q, Wang X

Received 21 December 2020

Accepted for publication 11 March 2021

Published 7 April 2021 Volume 2021:16 Pages 919—931

DOI https://doi.org/10.2147/COPD.S298465

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Richard Russell


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 China

Correspondence: Yingchun Zhao
Department of Cardiovascular Medicine, The First People’s Hospital of Lianyungang, No. 6 East Zhenhua Road, Haizhou, Lianyungang, Jiangsu, 222061, People’s Republic of China
Tel +86-0518-85767023
Email [email protected]

Background: 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

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