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Circ-OSBPL2 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-193a-5p/BRD4 Axis
Caifen Zheng1, Yongping Zhang2, Yingchun Zhao3
1Department of Respiratory and Critical Care Medicine, The First People's Hospital of Lianyungang, Lianyungang, People's Republic of China.
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.
Insights
Circular RNA oxysterol binding protein like 2 (circOSBPL2) promotes apoptosis, inflammation, and oxidative stress in chronic obstructive pulmonary disease (COPD) by sponging miR-193a-5p, which targets BRD4. This highlights circOSBPL2 as a potential therapeutic target for COPD.
Area of Science:
- Molecular Biology
- Respiratory Medicine
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in respiratory diseases.
- The specific role of circRNA oxysterol binding protein like 2 (circOSBPL2) in smoke-related chronic obstructive pulmonary disease (COPD) requires elucidation.
Purpose of the Study:
- To investigate the function of circOSBPL2 in the pathogenesis of smoke-related COPD.
- To explore the molecular mechanisms underlying circOSBPL2's role in COPD development.
Main Methods:
- Quantified expression of circOSBPL2, miR-193a-5p, and BRD4 using qRT-PCR and Western blot.
- Utilized cigarette smoke extract (CSE)-induced human bronchial epithelial cells (HBECs) to model COPD in vitro.
- Assessed cell apoptosis, inflammation (IL-6, IL-8, TNF-α), and oxidative stress (MDA, SOD) markers.
- Confirmed molecular interactions using dual-luciferase reporter and RNA immunoprecipitation assays.
Main Results:
- CircOSBPL2 expression was elevated in smokers and CSE-induced HBECs.
- circOSBPL2 knockdown attenuated CSE-induced cell injury, apoptosis, inflammation, and oxidative stress.
- circOSBPL2 acted as a sponge for miR-193a-5p, which directly targeted BRD4.
- The circOSBPL2/miR-193a-5p/BRD4 axis mediated CSE-induced human bronchial epithelial cell injury.
Conclusions:
- circOSBPL2 exacerbates apoptosis, inflammation, and oxidative stress in COPD via the miR-193a-5p/BRD4 pathway.
- circOSBPL2 represents a novel insight into COPD pathogenesis.
- circOSBPL2 inhibition offers a potential therapeutic strategy for COPD.
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