CircANKRD11 Knockdown Protects HPMECs from Cigarette Smoke Extract-Induced Injury by Regulating miR-145-5p/BRD4 Axis

Wang, Zheng; Zuo, Yuqiang; Gao, Zhihong

doi:10.2147/copd.s300332

Cited by 18 publications

(9 citation statements)

References 40 publications

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“…32 In addition, the protein mediated inflammatory gene NF-κB expression by combining with acetylated RELA. 33 Previous references have revealed that BRD4 interacts with circANKRD11/miR-145-5p axis 34 and the lncRNA MIR155HG/miR-128-5p pathway 35 to increase CSE-caused HPMEC damage in COPD. Meanwhile, Zheng et al 9 indicated that BRD4 could improve CSE-evoked human bronchial epithelial cell inflammation and oxidative stress promotion.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA 0000157 depletion protects human bronchial epithelioid cells from cigarette smoke extract-induced human bronchial epithelioid cell injury through the microRNA-149-5p/bromodomain containing 4 pathway

Song

et al. 2023

Hum Exp Toxicol

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Background Circular RNA (circRNA) has been reported to regulate respiratory diseases. In the study, we aimed to elucidate the role of circ_0000157 in smoke-related chronic obstructive pulmonary disease (COPD) and the inner mechanism. Methods COPD-like cell injury was induced by treating human bronchial epithelioid cells (16HBE) with cigarette smoke extract (CSE). The expression of circ_0000157, miR-149-5p, bromodomain containing 4 (BRD4), BCL2-associated x protein (Bax) and B-cell lymphoma-2 (Bcl-2) was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blotting. Enzyme-linked immunosorbent assay was performed to detect interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels. Malondialdehyde (MDA) production was detected by a lipid peroxidation MDA assay kit. Superoxide dismutase (SOD) activity was analyzed by a SOD activity assay kit. Results Circ_0000157 and BRD4 expression were upregulated, while miR-149-5p expression was downregulated in the blood of smokers with COPD and CSE-induced 16HBE cells compared with control groups. CSE treatment inhibited 16HBE cell proliferation and induced cell apoptosis, inflammation, and oxidative stress; however, these effects were remitted when circ_0000157 expression was decreased. In addition, circ_0000157 acted as a miR-149-5p sponge and regulated CSE-caused 16HBE cell damage by targeting miR-149-5p. The overexpression of BRD4, a target gene of miR-149-5p, attenuated the inhibitory effects of miR-149-5p introduction on CSE-induced cell damage. Further, circ_0000157 modulated BRD4 expression by associating with miR-149-5p in CSE-treated 16HBE cells. Conclusion Circ_0000157 knockdown ameliorated CSE-caused 16HBE cell damage by targeting the miR-149-5p/BRD4 pathway, providing a potential therapeutic strategy for clinic intervention in COPD.

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Section: Discussionmentioning

confidence: 99%

Circular RNA 0000157 depletion protects human bronchial epithelioid cells from cigarette smoke extract-induced human bronchial epithelioid cell injury through the microRNA-149-5p/bromodomain containing 4 pathway

Song

et al. 2023

Hum Exp Toxicol

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“…For instance, circANKRD11 is elevated in the lung samples of COPD patients, and knockdown of circANKRD11 ameliorated CSE-triggered cell apoptosis, oxidative stress, and inflammation in human pulmonary microvascular endothelial cells. 24 In addition, circ_0006892 is downregulated in lung tissue samples of COPD patients and CSE-treated bronchial epithelial cells, and upregulation of circ_0006892 weakened CSE-triggered apoptosis and inflammatory response 25 . However, the biological roles of most circRNAs in COPD have not been studied.…”

Section: Discussionmentioning

confidence: 99%

Circ_0040929 Serves as Promising Biomarker and Potential Target for Chronic Obstructive Pulmonary Disease

Miao¹,

Wu²,

Wu³

et al. 2022

COPD

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Background Circular RNAs (circRNAs) can act as essential regulators in many diseases, including chronic obstructive pulmonary disease (COPD). We aimed to explore the role and underlying mechanism of circ_0040929 in COPD. Methods A cellular model of COPD was constructed by treating human bronchial epithelial cells (16HBE) with cigarette smoke extract (CSE). The levels of circ_0040929, microRNA-515-5p (miR-515-5p) and insulin-like growth factor-binding protein 3 (IGFBP3) were measured by quantitative real-time PCR. Cell proliferation was assessed by Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine assays. Cell apoptosis was evaluated by flow cytometry. Protein expression was measured using Western blot assay. The levels of inflammatory factors and airway remodeling were assayed via enzyme-linked immunosorbent assay. The interaction between miR-515-5p and circ_0040929/IGFBP3 was confirmed by dual-luciferase reporter, RNA pull-down and RNA immunoprecipitation assays. Exosomes were detected using transmission electron microscopy. Results Circ_0040929 expression and IGFBP3 expression were upregulated in the serum of smokers (n = 22) compared to non-smokers (n = 22) and more significantly upregulated in the serum of COPD patients (n = 22). However, miR-515-5p expression was decreased in the serum of smokers compared to non-smokers and further reduced in the serum of COPD. Circ_0040929 knockdown attenuated CSE-induced cell injury by increasing proliferation and reducing apoptosis, inflammation, and airway remodeling in 16HBE cells. MiR-515-5p was a direct target of circ_0040929, and miR-515-5p inhibition reversed the effect of circ_0040929 knockdown in CSE-treated 16HBE cells. IGFBP3 was a direct target of miR-515-5p, and miR-515-5p overexpression alleviated CSE-induced cell injury via targeting IGFBP3. Moreover, circ_0040929 regulated IGFBP3 expression by targeting miR-515-5p. Importantly, circ_0040929 was upregulated in serum exosomes from COPD patients. Conclusion Circ_0040929 played a promoting role in CSE-induced COPD by regulating miR-515-5p/IGFBP3 axis, suggesting that it might be a novel potential target for COPD treatment.

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“…In COPD, several non-coding RNAs including circulating RNA (circRNA), long non-coding RNA (lncRNA), and miRNA have been reported to regulate airway epithelial cell apoptosis and inflammation induced by cigarette smoke. For example, both the circRNA ankyrin repeat domain 1 (circANKRD11) [55] and circRNA oxysterol binding protein like 2 (circOSBPL2) [56] were found to increase in the lungs of smokers with or without COPD. Downregulation of either mitigates cigarette smoke-induced apoptosis, inflammation, and oxidative stress in human bronchial epithelial cells.…”

Section: Chronic Obstructive Pulmonary Disease (Copd)mentioning

confidence: 99%

BRD4 as a Therapeutic Target in Pulmonary Diseases

Guo,

Olajuyin,

Tucker

et al. 2023

IJMS

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Bromodomain and extra-terminal domain (BET) proteins are epigenetic modulators that regulate gene transcription through interacting with acetylated lysine residues of histone proteins. BET proteins have multiple roles in regulating key cellular functions such as cell proliferation, differentiation, inflammation, oxidative and redox balance, and immune responses. As a result, BET proteins have been found to be actively involved in a broad range of human lung diseases including acute lung inflammation, asthma, pulmonary arterial hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD). Due to the identification of specific small molecular inhibitors of BET proteins, targeting BET in these lung diseases has become an area of increasing interest. Emerging evidence has demonstrated the beneficial effects of BET inhibitors in preclinical models of various human lung diseases. This is, in general, largely related to the ability of BET proteins to bind to promoters of genes that are critical for inflammation, differentiation, and beyond. By modulating these critical genes, BET proteins are integrated into the pathogenesis of disease progression. The intrinsic histone acetyltransferase activity of bromodomain-containing protein 4 (BRD4) is of particular interest, seems to act independently of its bromodomain binding activity, and has implication in some contexts. In this review, we provide a brief overview of the research on BET proteins with a focus on BRD4 in several major human lung diseases, the underlying molecular mechanisms, as well as findings of targeting BET proteins using pharmaceutical inhibitors in different lung diseases preclinically.

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CircANKRD11 Knockdown Protects HPMECs from Cigarette Smoke Extract-Induced Injury by Regulating miR-145-5p/BRD4 Axis

Cited by 18 publications

References 40 publications

Circular RNA 0000157 depletion protects human bronchial epithelioid cells from cigarette smoke extract-induced human bronchial epithelioid cell injury through the microRNA-149-5p/bromodomain containing 4 pathway

Circular RNA 0000157 depletion protects human bronchial epithelioid cells from cigarette smoke extract-induced human bronchial epithelioid cell injury through the microRNA-149-5p/bromodomain containing 4 pathway

Circ_0040929 Serves as Promising Biomarker and Potential Target for Chronic Obstructive Pulmonary Disease

BRD4 as a Therapeutic Target in Pulmonary Diseases

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