Analysis of expression profiles and bioinformatics suggests that plasma exosomal circular RNAs may be involved in ischemic stroke in the Chinese Han population

Metab Brain Dis. 2022 Mar;37(3):665-676. doi: 10.1007/s11011-021-00894-2. Epub 2022 Jan 24.

Abstract

Circular RNAs (circRNAs) have been confirmed to be associated with ischemic stroke(IS), but the involvement of exosomal circRNAs in plasma still needs to be extensively discussed. Therefore, we aimed to investigate the expression profile of exosomal circRNAs in plasma and the potential roles and mechanisms of exosomal circRNAs in the pathogenesis of ischemic stroke in the Chinese Han population. In this study, the plasma exosomal circRNA expression profiles of three IS patients and three healthy controls were analyzed using circRNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and circRNA-miRNA-mRNA regulatory network analysis were performed for the aberrantly expressed genes. Protein-protein interaction (PPI) networks and molecular complex detection algorithms (MCODEs) were analyzed by STRING and Cystoscope for functional annotation and construction, respectively. RNA-Seq analysis revealed that a total of 3540 circRNAs were aberrantly expressed in exosomes, 1177 circRNAs were significantly upregulated, and 2363 circRNAs were downregulated in IS patients compared to healthy controls. Bioinformatics analysis revealed that the parental genes of differentially expressed circRNAs as well as the mRNAs predicted in the circRNA-miRNA-mRNA regulatory network are enriched for signaling pathways associated with IS pathology, such as the MAPK signaling pathway, lipid and atherosclerosis, neurotrophic factor signaling pathways, mTOR signaling pathway, the p53 signaling pathway etc. Then, 10 hub genes were identified from the PPI and module networks, including FBXW11, FBXW7, UBE2V2, ANAPC7, CDC27, UBC, CDC5L, POLR2H, POLR2F and RBX1. Overall, the present study provides evidence of an altered plasma exosomal circRNA expression profile and its potential function in IS. Our findings may contribute to the study of the pathogenesis of circRNAs in IS and provide ideas for studying potential diagnostic biomarkers and therapeutic targets for IS.

Keywords: Circular RNA; Exosome; Ischemic stroke; Plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins
  • China
  • Computational Biology
  • Humans
  • Ischemic Stroke* / genetics
  • MicroRNAs* / genetics
  • RNA, Circular / genetics
  • RNA-Binding Proteins

Substances

  • CDC5L protein, human
  • Cell Cycle Proteins
  • MicroRNAs
  • RNA, Circular
  • RNA-Binding Proteins