Microarray Data Analysis of Molecular Mechanism Associated with Stroke Progression

J Mol Neurosci. 2019 Mar;67(3):424-433. doi: 10.1007/s12031-018-1247-3. Epub 2019 Jan 4.

Abstract

This study aimed to explore the molecular mechanism of stroke and provide a new target in the clinical management. The miRNA dataset GSE97532 (3 blood samples from middle cerebral artery occlusion (MCAO) and 3 from sham operation) and mRNA dataset GSE97533 (3 blood samples from MCAO and 3 from sham operation) were obtained from GEO database. Differentially expressed mRNA (DEGs) and miRNAs (DEMIRs) were screened out between MCAO and sham operation groups. Then, DEMIR-DEG interactions were explored and visualized using Cytoscape software. Moreover, the enrichment analysis was performed on these DEMIRs and DEGs. Furthermore, protein-protein interaction (PPI) network was constructed. Finally, the DEG-target transcription factors (TFs) were investigated using the WebGestal software. The current bioinformatics analysis revealed 38 DEMIRs and 546 DEGs between MCAO and sham operation groups. The DEMIR-DEG analysis revealed 370 relations, such as miR-107-5p-Furin. The top 10 up- and downregulated DEMIRs were mainly enriched in pathways like cAMP signaling pathway. The PPI network analysis revealed 2 modules. The target DEGs of the 10 up- and downregulated DEMIRs in 2 modules were mainly assembled in functions like ATP binding and pathway including ABC transporters. Furthermore, the DEG-TF network analysis identified 5 outstanding TFs including androgen receptor (AR). miR107-5p might take part in the progression of stroke via inhibiting the expression of Furin. TFs like AR might be used as a novel gene therapy target for stroke. Furthermore, cAMP signaling pathway and ATP binding function might be a novel breakthrough for stroke treatment.

Keywords: Differentially expressed mRNA; Differentially expressed miRNA; Function and pathway analysis; Stroke; Transcription factors.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Down-Regulation
  • Gene Regulatory Networks
  • Infarction, Middle Cerebral Artery / blood
  • Infarction, Middle Cerebral Artery / genetics*
  • Infarction, Middle Cerebral Artery / metabolism
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Protein Interaction Maps
  • RNA, Messenger / blood
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Rats
  • Signal Transduction

Substances

  • Biomarkers
  • MicroRNAs
  • RNA, Messenger