The alterations of circular RNA expression in plasma exosomes from patients with schizophrenia

J Cell Physiol. 2021 Jan;236(1):458-467. doi: 10.1002/jcp.29873. Epub 2020 Jun 15.

Abstract

Schizophrenia (SZ) is characterized by a high morbidity and disability rate and has gradually increased in rate and caused much burden. However, the pathogenesis of SZ is elusive and may include changes in the biological molecules in exosomes. In this study, we first compared the alterations of plasma exosomal circular RNAs (exo-circRNAs) from SZ patients and matched health controls by high-throughput sequencing. We further explored whether plasma exo-circRNAs can be estimable targets for researching the pathogenesis, potential diagnostic biomarkers, and therapeutic strategy of SZ. A total of 44 plasma exo-circRNAs were differentially expressed between SZ patients and matched Health Controls, including 38 upregulated circRNAs and six downregulated circRNAs (fold change ≥2; p < .05). Eight differentially expressed circRNAs were verified by quantitative real-time polymerase chain reaction, and four out of eight circRNAs were positively confirmed and contained binding sites to many microRNAs. Bioinformatics analysis, including Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, showed that these differentially expressed circRNAs played potential roles in pathogenesis, especially regarding the metabolic process, stress response, and histone ubiquitination. In conclusion, this study supplies a new window for understanding the pathogenesis of SZ at molecular levels, and serves as a tool for better exploring potential diagnostic biomarkers and the therapeutic strategy for SZ.

Keywords: circular RNA; high-throughput sequencing; pathogenesis; plasma exosomes; schizophrenia.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Binding Sites / genetics
  • Biomarkers / metabolism
  • Down-Regulation / genetics
  • Exosomes / genetics*
  • Female
  • Gene Expression Profiling / methods
  • Histones / genetics
  • Humans
  • Male
  • MicroRNAs / genetics
  • Middle Aged
  • RNA, Circular / genetics*
  • Schizophrenia / genetics*
  • Ubiquitination / genetics
  • Up-Regulation / genetics
  • Young Adult

Substances

  • Biomarkers
  • Histones
  • MicroRNAs
  • RNA, Circular