Idiopathic Pulmonary Fibrosis Molecular Substrates Revealed by Competing Endogenous RNA Regulatory Networks

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic disease of the lung with poor prognosis. Fibrosis results from remodeling of the interstitial tissue. A wide range of gene expression changes are observed, but the role of micro RNAs (miRNAs) and circular RNAs (circRNA) is still unclear. Therefore, this study aimed to establish an messenger RNA (mRNA)-miRNA-circRNA competing endogenous RNA (ceRNA) regulatory network to uncover novel molecular signatures using systems biology tools. Six datasets were used to determine differentially expressed genes (DEGs) and miRNAs (DEmiRNA). Accordingly, protein-protein, mRNA-miRNA, and miRNA-circRNA interactions were constructed. Modules were determined and further analyzed in the Drug Gene Budger platform to identify potential therapeutic compounds. We uncovered common 724 DEGs and 278 DEmiRNAs. In the protein-protein interaction network, TMPRSS4, ESR2, TP73, CLEC4E, and TP63 were identified as hub protein coding genes. The mRNA-miRNA interaction network revealed two modules composed of ADRA1A, ADRA1B, hsa-miR-484 and CDH2, TMPRSS4, and hsa-miR-543. The DEmiRNAs in the modules further analyzed to propose potential circRNA regulators in the ceRNA network. These results help deepen the understanding of the mechanisms of IPF. In addition, the molecular leads reported herein might inform future innovations in diagnostics and therapeutics research and development for IPF.

Automated summary

To uncover novel molecular signatures of idiopathic pulmonary fibrosis (IPF), this study established a regulatory network involving messenger RNA (mRNA), micro RNAs (miRNAs), and circular RNAs (circRNA). Through analysis of multiple datasets, differentially expressed genes (DEGs) and miRNAs (DEmiRNA) were identified, and interactions between proteins, mRNA-miRNA, and miRNA-circRNA were constructed. The findings deepen our understanding of IPF mechanisms and offer potential leads for diagnostics and therapeutics research and development.