Construction of a TFs-miRNA-mRNA network related to idiopathic pulmonary fibrosis

Abstract

Background: The transcription factors (TFs)-miRNA-mRNA network plays an important role in a variety of diseases. The TFs-miRNA-mRNA network related to idiopathic pulmonary fibrosis (IPF) remains unclear.Methods: GSE110147 and GSE53845 datasets from GEO database were used to process differential gene (DEGs) analysis, GSEA, WGCNA, Gene ontology and KEGG analysis. GSE13316 dataset were used to perform differential miRNA (DEMs) analysis and TFs prediction. Finally, a TFs-miRNA-mRNA network related to IPF was constructed, and the function was performed by GO and KEGG analysis. And twenty TFs in the network were verified by qPCR.Results: Through our analysis, 53 DEMs and 3675 DEGs were screened. The GSEA results suggested these genes were mainly related to protein digestion and absorption. WGCNA results showed that these DEGs were divided into eight modules, and the GO and KEGG analysis results of turquoise module genes showed that these 69 turquoise module genes were mainly enriched in metabolism. Besides, a TFs-miRNA-mRNA network, including 35 TFs, 12 miRNAs and 84 mRNAs, was constructed. Ultimately, the functional enrichment analysis showed that the TFs-miRNA-mRNA network mainly related to microtubule pathway, apoptotic signaling pathway and PI3K-Akt signaling pathway. Furthermore, experimental verification for TFs showed ARNTL, TRIM28, EZH2, BCOR and ASXL1 were sufficiently up-regulated in TGF-β1 treatment groups, while BCL6, BHLHE40, FOXA1 and EGR1 were significantly down-regulated. Conclusions: The novel TFs-miRNA-mRNA network that we constructed could provide new insights into the underlying molecular mechanisms of IPF. ARNTL, TRIM28, EZH2, BCOR, ASXL1, BCL6, BHLHE40, FOXA1 and EGR1 may play important role in IPF and become effective biomarker for diagnosis and treatment.