Circ_0040929 Serves as Promising Biomarker and Potential Target for Chronic Obstructive Pulmonary Disease
Yi Miao,1 Junfang Wu,1 Runmiao Wu,1 Enguang Wang,2 Jing Wang3 1Department of Respiratory Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, 710068, People’s Republic of China; 2Department of Respiratory and Critical Care, the Fifth Affiliated Hospital of Xinjia...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2022-09-01
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| Series: | International Journal of COPD |
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| Online Access: | https://www.dovepress.com/circ0040929-serves-as-promising-biomarker-and-potential-target-for-chr-peer-reviewed-fulltext-article-COPD |
| _version_ | 1798001875418611712 |
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| author | Miao Y Wu J Wu R Wang E Wang J |
| author_facet | Miao Y Wu J Wu R Wang E Wang J |
| author_sort | Miao Y |
| collection | DOAJ |
| description | Yi Miao,1 Junfang Wu,1 Runmiao Wu,1 Enguang Wang,2 Jing Wang3 1Department of Respiratory Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, 710068, People’s Republic of China; 2Department of Respiratory and Critical Care, the Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi City, 830000, People’s Republic of China; 3Department of Clinical Laboratory, Shaanxi Provincial People’s Hospital, Xi’an City, 710068, People’s Republic of ChinaCorrespondence: Junfang Wu, Department of Respiratory Medicine, Shaanxi Provincial People’s Hospital, No. 256, West Youyi Road, Beilin District, Xi’an City, Shaanxi Province, People’s Republic of China, Tel +86 29-85251331, Email wujunfang1114@163.comBackground: 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.Keywords: chronic obstructive pulmonary disease, circ_0040929, miR-515-5p, IGFBP3 |
| first_indexed | 2024-04-11T11:44:15Z |
| format | Article |
| id | doaj.art-37e0577e0ab24836b24b3698eef94404 |
| institution | Directory Open Access Journal |
| issn | 1178-2005 |
| language | English |
| last_indexed | 2024-04-11T11:44:15Z |
| publishDate | 2022-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of COPD |
| spelling | doaj.art-37e0577e0ab24836b24b3698eef944042022-12-22T04:25:43ZengDove Medical PressInternational Journal of COPD1178-20052022-09-01Volume 172079209278019Circ_0040929 Serves as Promising Biomarker and Potential Target for Chronic Obstructive Pulmonary DiseaseMiao YWu JWu RWang EWang JYi Miao,1 Junfang Wu,1 Runmiao Wu,1 Enguang Wang,2 Jing Wang3 1Department of Respiratory Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, 710068, People’s Republic of China; 2Department of Respiratory and Critical Care, the Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi City, 830000, People’s Republic of China; 3Department of Clinical Laboratory, Shaanxi Provincial People’s Hospital, Xi’an City, 710068, People’s Republic of ChinaCorrespondence: Junfang Wu, Department of Respiratory Medicine, Shaanxi Provincial People’s Hospital, No. 256, West Youyi Road, Beilin District, Xi’an City, Shaanxi Province, People’s Republic of China, Tel +86 29-85251331, Email wujunfang1114@163.comBackground: 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.Keywords: chronic obstructive pulmonary disease, circ_0040929, miR-515-5p, IGFBP3https://www.dovepress.com/circ0040929-serves-as-promising-biomarker-and-potential-target-for-chr-peer-reviewed-fulltext-article-COPDchronic obstructive pulmonary diseasecirc_0040929mir-515-5pigfbp3 |
| spellingShingle | Miao Y Wu J Wu R Wang E Wang J Circ_0040929 Serves as Promising Biomarker and Potential Target for Chronic Obstructive Pulmonary Disease International Journal of COPD chronic obstructive pulmonary disease circ_0040929 mir-515-5p igfbp3 |
| title | Circ_0040929 Serves as Promising Biomarker and Potential Target for Chronic Obstructive Pulmonary Disease |
| title_full | Circ_0040929 Serves as Promising Biomarker and Potential Target for Chronic Obstructive Pulmonary Disease |
| title_fullStr | Circ_0040929 Serves as Promising Biomarker and Potential Target for Chronic Obstructive Pulmonary Disease |
| title_full_unstemmed | Circ_0040929 Serves as Promising Biomarker and Potential Target for Chronic Obstructive Pulmonary Disease |
| title_short | Circ_0040929 Serves as Promising Biomarker and Potential Target for Chronic Obstructive Pulmonary Disease |
| title_sort | circ 0040929 serves as promising biomarker and potential target for chronic obstructive pulmonary disease |
| topic | chronic obstructive pulmonary disease circ_0040929 mir-515-5p igfbp3 |
| url | https://www.dovepress.com/circ0040929-serves-as-promising-biomarker-and-potential-target-for-chr-peer-reviewed-fulltext-article-COPD |
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