Potentially critical roles of TNPO1, RAP1B, ZDHHC17, and PPM1B in the progression of coronary atherosclerosis through microarray data analysis

J Cell Biochem. 2019 Mar;120(3):4301-4311. doi: 10.1002/jcb.27715. Epub 2018 Sep 30.

Abstract

Objective: This study aimed to identify more potentially critical genes associated with atherosclerotic coronary artery disease (CAD).

Materials and methods: Gene expression profile of GSE12288 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened in atherosclerotic CAD samples compared with controls, followed by weighed gene coexpression network analysis (WGCNA) by which the most significant module was identified. Gene coexpression network was constructed based on genes in the most significant module, and functional annotation was also performed. In addition, microRNAs (miRNAs) that were directly associated with CAD were screened from the literature, and the miRNA-target regulatory network was constructed based on genes in the most significant module, followed by Gene Ontology (GO) and pathway enrichment analysis. Furthermore, we used another data set of GSE42148 from the GEO database to perform data validation.

Results: WGCNA analysis showed that the turquoise module may have the most important role in atherosclerotic CAD. Genes in this module were involved in translational elongation and intracellular signal transduction. Besides, we identified five confirmed CAD-related miRNAs. TNPO1, RAP1B, and ZDHHC17 could be targeted by four of these miRNAs. Genes such as PPM1B could be regulated by three miRNAs. Moreover, TNPO1 and ZDHHC17 were involved in the GO terms associated with protein localization and transport and the immune system; RAP1B and PPM1B were linked with intracellular signal transduction-related pathways. In addition, PPM1B and ZDHHC17 had accordantly significant expression changes in another data set GSE42148.

Conclusion: TNPO1, RAP1B, ZDHHC17, and PPM1B may play essential roles in the progression of coronary atherosclerosis.

Keywords: Atherosclerotic coronary artery disease (CAD); differentially expressed genes (DEG); functional enrichment analysis; weighed gene coexpression network analysis (WGCNA).

MeSH terms

  • Acyltransferases / genetics*
  • Adaptor Proteins, Signal Transducing / genetics*
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / pathology
  • Data Analysis*
  • Databases, Genetic
  • Disease Progression*
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / genetics
  • Nerve Tissue Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Protein Interaction Maps
  • Protein Phosphatase 2C / genetics*
  • Signal Transduction / genetics
  • Transcriptome*
  • beta Karyopherins / genetics*
  • rap GTP-Binding Proteins / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • MicroRNAs
  • Nerve Tissue Proteins
  • TNPO1 protein, human
  • beta Karyopherins
  • Acyltransferases
  • ZDHHC17 protein, human
  • PPM1B protein, human
  • Protein Phosphatase 2C
  • RAP1B protein, human
  • rap GTP-Binding Proteins