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Refined Murine Model of Idiopathic Pulmonary Fibrosis
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Construction of a TFs-miRNA-mRNA network related to idiopathic pulmonary fibrosis

Minhong Su1, Junfang Liu1, Xiping Wu1

  • 1Department of Respiratory and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Annals of Translational Medicine
|February 23, 2023
PubMed
Abstract

Insights

This study constructed a novel transcription factor-microRNA-messenger RNA network for idiopathic pulmonary fibrosis (IPF). Specific genes identified in this network may serve as crucial biomarkers for IPF diagnosis and treatment.

Area of Science:

  • Molecular Biology
  • Genomics
  • Systems Biology

Background:

  • The interplay between transcription factors (TFs), microRNAs (miRNAs), and messenger RNAs (mRNAs) is critical in disease pathogenesis.
  • The specific molecular network governing idiopathic pulmonary fibrosis (IPF) remains incompletely understood.

Purpose of the Study:

  • To elucidate the TFs-miRNA-mRNA regulatory network implicated in IPF.
  • To identify potential molecular biomarkers for IPF diagnosis and therapeutic intervention.

Main Methods:

  • Utilized Gene Expression Omnibus (GEO) datasets (GSE110147, GSE53845, GSE13316) for differential gene and miRNA expression analysis.
  • Applied Weighted Gene Co-expression Network Analysis (WGCNA), Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
  • Constructed and functionally evaluated a TFs-miRNA-mRNA network, with key TF expression validated via quantitative real-time polymerase chain reaction (qRT-PCR).

Main Results:

  • Identified 53 differentially expressed miRNAs (DEMs) and 2,630 differentially expressed genes (DEGs).
  • Constructed a regulatory network comprising 25 TFs, 11 miRNAs, and 60 mRNAs, significantly associated with cell cycle and PI3K-Akt signaling pathways.
  • Validated differential expression of nine key TFs (e.g., ARNTL, EZH2, BCL6) in response to TGF-β1 stimulation.

Conclusions:

  • A novel TFs-miRNA-mRNA network provides new insights into IPF molecular mechanisms.
  • Identified TFs, including ARNTL, TRIM28, EZH2, BCOR, ASXL1, BCL6, BHLHE40, FOXA1, and EGR1, as potential diagnostic and therapeutic biomarkers for IPF.
Keywords:
Idiopathic pulmonary fibrosis (IPF)biomarkernetworktranscription factors (TFs)weighted gene co-expression network analysis (WGCNA)

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