Open Access

Transcriptomic analysis and validation study of key genes and the HIF‑1α/HO‑1 pathway associated with ferroptosis in neutrophilic asthma

  • Authors:
    • Lu Lin
    • Zenghua Liao
    • Yinghua Li
    • Shitong Pan
    • Sihui Wu
    • Qi-Xiang Sun
    • Chaoqian Li
  • View Affiliations

  • Published online on: September 19, 2024     https://doi.org/10.3892/etm.2024.12722
  • Article Number: 433
  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ferroptosis, as a unique form of cell death caused by iron overload and lipid peroxidation, is involved in the pathogenesis of various inflammatory diseases of the airways. Inhibition of ferroptosis has become a novel strategy for reducing airway epithelial cell death and improving airway inflammation. The aim of the present study was to analyze and validate the key genes and signaling pathways associated with ferroptosis by bioinformatic methods combined with experimental analyzes in vitro and in vivo to aid the diagnosis and treatment of neutrophilic asthma. A total of 1,639 differentially expressed genes (DEGs) were identified in the transcriptome dataset. After overlapping with ferroptosis‑related genes, 11 differentially expressed ferroptosis‑related genes (DE‑FRGs) were obtained. A new diagnostic model was constructed by these DE‑FRGs from the transcriptome dataset with those from the GSE108417 dataset. The receiver operating characteristic curve analysis indicated that the area under the curve had good diagnostic performance (>0.8). As a result, four key DE‑FRGs (CXCL2, HMOX1, IL‑6 and SLC7A5) and biological pathway [hypoxia‑inducible factor 1 (HIF‑1) signaling pathway] associated with ferroptosis in neutrophilic asthma were identified by the bioinformatics analysis combined with experimental validation. The upstream regulatory network of key DE‑FRGs and target drugs were predicted and the molecular docking results from screened 37 potential therapeutic drugs revealed that the 13 small‑molecule drugs exhibited a higher stable binding to the primary proteins of key DE‑FRGs. The results suggested that four key DE‑FRGs and the HIF‑1α/heme oxygenase 1 pathway associated with ferroptosis have potential as novel markers or targets for the diagnosis or treatment of neutrophilic asthma.
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December-2024
Volume 28 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Lin L, Liao Z, Li Y, Pan S, Wu S, Sun Q and Li C: Transcriptomic analysis and validation study of key genes and the HIF‑1α/HO‑1 pathway associated with ferroptosis in neutrophilic asthma. Exp Ther Med 28: 433, 2024.
APA
Lin, L., Liao, Z., Li, Y., Pan, S., Wu, S., Sun, Q., & Li, C. (2024). Transcriptomic analysis and validation study of key genes and the HIF‑1α/HO‑1 pathway associated with ferroptosis in neutrophilic asthma. Experimental and Therapeutic Medicine, 28, 433. https://doi.org/10.3892/etm.2024.12722
MLA
Lin, L., Liao, Z., Li, Y., Pan, S., Wu, S., Sun, Q., Li, C."Transcriptomic analysis and validation study of key genes and the HIF‑1α/HO‑1 pathway associated with ferroptosis in neutrophilic asthma". Experimental and Therapeutic Medicine 28.6 (2024): 433.
Chicago
Lin, L., Liao, Z., Li, Y., Pan, S., Wu, S., Sun, Q., Li, C."Transcriptomic analysis and validation study of key genes and the HIF‑1α/HO‑1 pathway associated with ferroptosis in neutrophilic asthma". Experimental and Therapeutic Medicine 28, no. 6 (2024): 433. https://doi.org/10.3892/etm.2024.12722