Related Experiment Video
Updated: Sep 16, 2025
Author Spotlight: Advancing the Analysis of Plasma Extracellular Vesicle Proteome for Cardiovascular Biomarker Studies
Published on: January 31, 2025
CircRNA-miRNA-mRNA networks in plasma extracellular vesicles as biomarkers for first-onset schizophrenia
Xinzhe Du1,2, Wei Hu3, Xinrong Li1
1Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China.
Background:
The circRNA-miRNA-mRNA networks of extracellular vesicles (EVs) in first-onset schizophrenia (FOS) have not been reported yet. Here, we constructed circRNA-miRNA-mRNA networks of EVs, and examined their diagnostic efficiency in FOS.
Methods:
The expression levels of circRNAs, miRNAs and mRNAs in EVs derived from 10 FOS patients and 10 healthy controls (HC) were determined by high-throughput sequencing. The circRNA-miRNA-mRNA networks was constructed based on the overlapped miRNAs between differentially expressed (DE) miRNAs and circRNA-targted miRNAs, and overlapped mRNAs between DE-mRNAs and miRNA-targeted mRNAs. Gene expression levels were validated using quantitative real-time PCR in 31 FOS and 31 HC cases. Receiver operating characteristic (ROC) curve analysis was performed to examine the diagnostic efficacy. Correlation analysis was performed using Pearson's or Spearman's correlation coefficient.
Results:
There were 26,194 DE-circRNAs, 22 DE-miRNAs, and 2637 DE-mRNAs in plasma EVs of FOS patients. Then, the circRNA-miRNA-mRNA networks consisting of 9 circRNA, 6 miRNA and 16 mRNA, were constructed. Three network (chr15:93496587-93499879+-hsa-miR-20b-5p-ANKH; chr7:40037093-40087476+-hsa-miR-22-3p-C5orf24; and chr19:17883266-17883550+-hsa-miR-502-3p-B4GALT5) were selected for further investigation. The expression levels of 9 genes in validation data were consistent with the results of the high-throughput sequencing. The area under the ROC curve (AUC) of the circRNA-miRNA-mRNA network was higher than that of circRNA, miRNA or mRNA alone in plasma EVs, and the AUC of mRNAs in plasma EVs was higher than that of mRNAs in peripheral blood. The expression levels of chr15:93496587-93,499,879+, chr7:40037093-40,087,476+, hsa-miR-22-3p and B4GALT5 were correlated with the PANSS score.
Conclusion:
We constructed the circRNA-miRNA-mRNA networks of plasma EVs in FOS, demonstrating their potential as a biomarker for FOS.
Insights
This study reveals novel circular RNA-microRNA-messenger RNA networks in extracellular vesicles for first-onset schizophrenia (FOS). These networks show promise as diagnostic biomarkers for FOS, outperforming individual molecule detection.
Area of Science:
- Molecular biology
- Genomics
- Biomarker discovery
Background:
- Extracellular vesicles (EVs) and their molecular cargo are increasingly recognized in neurological disorders.
- CircRNA-miRNA-mRNA interactions are crucial in gene regulation but remain underexplored in first-onset schizophrenia (FOS) EVs.
Purpose of the Study:
- To construct and analyze circRNA-miRNA-mRNA networks in EVs from individuals with FOS.
- To evaluate the diagnostic efficiency of these networks for FOS.
Main Methods:
- High-throughput sequencing of circRNAs, miRNAs, and mRNAs from plasma EVs of FOS patients and healthy controls.
- Construction of circRNA-miRNA-mRNA networks based on differential expression and predicted interactions.
- Validation of gene expression using quantitative real-time PCR and diagnostic efficacy assessment via ROC curve analysis.
Main Results:
- Identified extensive differentially expressed circRNAs, miRNAs, and mRNAs in FOS patient EVs.
- Constructed comprehensive circRNA-miRNA-mRNA networks, highlighting key regulatory interactions.
- The integrated network demonstrated superior diagnostic accuracy for FOS compared to individual molecular types, with EV-derived mRNA showing higher efficacy than peripheral blood mRNA.
Conclusions:
- Established circRNA-miRNA-mRNA networks within plasma EVs as a potential diagnostic biomarker signature for FOS.
- Specific network components correlate with clinical severity, suggesting their utility in disease monitoring.
Related Concept Videos
01:29Biological Causes of Schizophrenia
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
01:36Overview of Exosomes
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...