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lncRNA GAS5 promotes pyroptosis in COPD by functioning as a ceRNA to regulate the miR‑223‑3p/NLRP3 axis

  • Authors:
    • Rubing Mo
    • Jing Li
    • Yongxing Chen
    • Yipeng Ding
  • View Affiliations / Copyright

    Affiliations: Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, P.R. China, Department of Emergency, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, P.R. China, Department of General Practice, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, P.R. China
    Copyright: © Mo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 219
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    Published online on: May 13, 2022
       https://doi.org/10.3892/mmr.2022.12735
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Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible and progressive airflow limitation and encompasses a spectrum of diseases, including chronic obstructive bronchitis and emphysema. Pyroptosis is a unique form of inflammatory cell death mediated by the activation of caspase‑1 and inflammasomes. The long non‑coding RNA (lncRNA) growth arrest‑specific 5 (GAS5) is a well‑documented tumor suppressor, which is associated with cell proliferation and death in various diseases. The aim of the present study was to evaluate whether lncRNA GAS5 is associated with the pyroptosis in COPD. To create a COPD cell model, MRC‑5 cells were treated with 10 µg/ml lipopolysaccharide (LPS) for 48 h. Then the level of pro‑caspase 1, caspase 1, IL‑1β, IL‑18, NLRP3 and cleaved gasdermin D (GSDMD) was examined by western blotting. GAS5 mRNA level was detected by qualitative PCR following LPS treatment in MRC‑5 cells. Subsequently, IL‑2, IL‑6, IL‑10 and TNF‑α in MRC‑5 cells was measured by ELISA. Then the proliferation ability of MRC‑5 cells was detected by CCK‑8. Cell death was detected by TUNEL assay. LDH release was measured using an LDH Cytotoxicity Assay kit. The Magna RIP kit was used to validate the interaction between GAS5 and miR‑223‑3p. The present study revealed that increased expression levels of caspase‑1, IL‑1β, IL‑18 and cleaved GSDMD were observed in LPS‑treated MRC‑5 cells, indicating that pyroptosis is involved in COPD progression. Additionally, LPS induced the increase in GAS5 mRNA expression levels and the release of inflammatory factors (IL‑2, IL‑6, IL‑10 and TNF‑α), suggesting that GAS5 is implicated in pyroptosis in COPD. Furthermore, upregulation of GAS5 promoted cell death and inhibited proliferation in the MRC‑5 cell line. Additionally, increased GAS5 expression significantly promoted the production of caspase‑1, IL‑1β, IL‑18, cleaved GSDMD and NLR pyrin domain containing protein 3 (NLRP3). A dual‑luciferase assay demonstrated that GAS5 could directly bind to microRNA‑223‑3p (miR‑223‑3p), and NLRP3 is a direct target of miR‑223‑3p. Furthermore, GAS5 reduced the expression levels of miR‑223‑3p, while it increased the expression levels of NLRP3. The present study concluded that lncRNA GAS5 promoted pyroptosis in COPD by targeting the miR‑223‑3p/NLRP3 axis, implying that GAS5 could be a potential target for COPD.
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Copy and paste a formatted citation
Spandidos Publications style
Mo R, Li J, Chen Y and Ding Y: lncRNA GAS5 promotes pyroptosis in COPD by functioning as a ceRNA to regulate the miR‑223‑3p/NLRP3 axis. Mol Med Rep 26: 219, 2022.
APA
Mo, R., Li, J., Chen, Y., & Ding, Y. (2022). lncRNA GAS5 promotes pyroptosis in COPD by functioning as a ceRNA to regulate the miR‑223‑3p/NLRP3 axis. Molecular Medicine Reports, 26, 219. https://doi.org/10.3892/mmr.2022.12735
MLA
Mo, R., Li, J., Chen, Y., Ding, Y."lncRNA GAS5 promotes pyroptosis in COPD by functioning as a ceRNA to regulate the miR‑223‑3p/NLRP3 axis". Molecular Medicine Reports 26.1 (2022): 219.
Chicago
Mo, R., Li, J., Chen, Y., Ding, Y."lncRNA GAS5 promotes pyroptosis in COPD by functioning as a ceRNA to regulate the miR‑223‑3p/NLRP3 axis". Molecular Medicine Reports 26, no. 1 (2022): 219. https://doi.org/10.3892/mmr.2022.12735
Copy and paste a formatted citation
x
Spandidos Publications style
Mo R, Li J, Chen Y and Ding Y: lncRNA GAS5 promotes pyroptosis in COPD by functioning as a ceRNA to regulate the miR‑223‑3p/NLRP3 axis. Mol Med Rep 26: 219, 2022.
APA
Mo, R., Li, J., Chen, Y., & Ding, Y. (2022). lncRNA GAS5 promotes pyroptosis in COPD by functioning as a ceRNA to regulate the miR‑223‑3p/NLRP3 axis. Molecular Medicine Reports, 26, 219. https://doi.org/10.3892/mmr.2022.12735
MLA
Mo, R., Li, J., Chen, Y., Ding, Y."lncRNA GAS5 promotes pyroptosis in COPD by functioning as a ceRNA to regulate the miR‑223‑3p/NLRP3 axis". Molecular Medicine Reports 26.1 (2022): 219.
Chicago
Mo, R., Li, J., Chen, Y., Ding, Y."lncRNA GAS5 promotes pyroptosis in COPD by functioning as a ceRNA to regulate the miR‑223‑3p/NLRP3 axis". Molecular Medicine Reports 26, no. 1 (2022): 219. https://doi.org/10.3892/mmr.2022.12735
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