circRNA-associated-ceRNA networks in patients with traumatic tracheal stenosis

TL;DR

This study explores circRNA networks in traumatic tracheal stenosis patients to identify potential biomarkers and understand disease mechanisms.

Contribution

The study establishes a circRNA-associated ceRNA network in traumatic tracheal stenosis, offering new insights into its pathogenesis.

Findings

603 circRNAs and 1950 mRNAs were differentially expressed in TTS patients compared to controls.

A ceRNA network involving 17 circRNAs, 7 miRNAs, and 9 mRNAs was established and validated.

S100A2 and circ_030284 were upregulated, while miR-1207-5p was downregulated in TTS patients.

Abstract

Traumatic tracheal stenosis (TTS) is one of the most commonly seen iatrogenic airway injuries caused by tracheal intubation or tracheotomy, which can harm the lives of patients in severe cases. Circular RNA (circRNA) is related to a variety of human diseases. However, the role that circRNAs are likely to play in traumatic tracheal stenosis is not known to a large extent till now. This research is designed to identify potential biomarkers and learn more about the mechanism of TTS through the establishment of a circRNA-associated ceRNA network. By carrying out RNA sequencing (RNA-seq), the expression profiles of circRNAs and mRNAs were explored from four TTS patients and four normal control cases. To investigate the differentially expressed circRNAs and mRNAs, this research performed both Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A circRNA-miRNA-mRNA network was predicted and established using bioinformatics tools including Mireap, Miranda, TargetScan, the circBase database, and miRTarBase. And then verified by utilizing RT-qPCR assays from six TTS patients and six normal control cases. In clinical tissue samples of the TTS group and the control group, 603 circRNAs and 1950 mRNAs were differentially expressed. According to GO and KEGG analyses, the differentially expressed circRNAs mainly participated in lysine degradation, platelet activation, and the VEGF/HIF-1 signaling pathway, whereas the differentially expressed mRNAs mainly participated in cytokine-cytokine receptor interaction, ECM-receptor interaction, neutrophil extracellular trap formation, and the PI3K-Akt signaling pathway. By utilizing 17 circRNAs, 7 miRNAs, and 9 mRNAs, a competing endogenous RNA (ceRNA) network was set up. Using RT-qPCR assay, It was confirmed that S100A2 and circ_030284 were upregulated, while miR-1207-5p was downregulated in TTS patients compared to normal controls, consistent with the gene chip outcomes. The research presents a comprehensive circRNA-associated ceRNA network in patients with TTS, which provides novel insights into TTS’s underlying pathogenesis.

The online version contains supplementary material available at 10.1038/s41598-025-24740-y.

Figures