Abnormal expression of TGFBR2, EGF, LRP10, and IQGAP1 is involved in the pathogenesis of coronary artery disease

Rev Cardiovasc Med. 2021 Sep 24;22(3):947-958. doi: 10.31083/j.rcm2203103.

Abstract

Coronary artery disease (CAD) is the most common cardiovascular disease worldwide. In this study, we investigated the pathogenesis of CAD. We downloaded the GSE98583 dataset, including 12 CAD samples and 6 normal samples, from the Gene Expression Omnibus (GEO) database and screened differentially expressed genes (DEGs) in CAD versus normal samples. Next, we performed functional enrichment analysis, protein-protein interaction (PPI) network, and functional module analyses to explore potential functions and regulatory functions of identified DEGs. Next, transcription factors (TFs) and microRNAs (miRNAs) targeting DEGs were predicted. In total, 456 DEGs were identified in CAD and normal samples, including 175 upregulated and 281 downregulated genes. These genes were enriched in the intestinal immune network for immunoglobulin A production and the mitogen-activated protein kinase signaling pathway (e.g., TGFBR2 and EGF). The PPI network contained 212 genes, and HIST1H2BJ, HIST1H2AC, EGF, and EP300 were hub genes with degrees higher than 10. Four significant modules were identified from the PPI network, with genes in the modules mainly enriched in the inflammatory response, protein ubiquitination involved in ubiquitin-dependent protein catabolic processes, protein transport, and mitochondrial translational elongation, respectively. Two TFs (E2F1 and FOXK1) and five miRNAs (miR-122A, miR-516-5P, miR-507, miR-342, and miR-520F) were predicted to target 112 DEGs. miR-122A reportedly targets both LRP10 and IQGAP1 in the TF-miRNA target regulatory network. The abnormal expression of TGFBR2, EGF, LRP10, and IQGAP1 may be implicated in CAD pathogenesis. Our study provides targets and potential regulators for investigating CAD pathogenesis.

Keywords: Coronary artery disease; MAPK signaling pathway; Pathogenesis; Transcription factor; microRNAs.

MeSH terms

  • Coronary Artery Disease* / genetics
  • Epidermal Growth Factor*
  • Forkhead Transcription Factors
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Humans
  • Receptor, Transforming Growth Factor-beta Type II
  • ras GTPase-Activating Proteins

Substances

  • FOXK1 protein, human
  • Forkhead Transcription Factors
  • IQ motif containing GTPase activating protein 1
  • ras GTPase-Activating Proteins
  • Epidermal Growth Factor
  • Receptor, Transforming Growth Factor-beta Type II