TY - JOUR
T1 - CircRNA-miRNA-mRNA networks in plasma extracellular vesicles as biomarkers for first-onset schizophrenia
AU - Du, Xinzhe
AU - Hu, Wei
AU - Li, Xinrong
AU - Gao, Yao
AU - Li, Junxia
AU - Hu, Xiaodong
AU - Wang, Xiao
AU - Zhao, Wentao
AU - Cheng, Long
AU - Cao, Xiaohua
AU - Cao, Hongbao
AU - Ren, Zhiyong
AU - Zhang, Yu
AU - Xu, Yong
AU - Liu, Sha
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
KW - Extracellular vesicles
KW - ROC
KW - Schizophrenia
KW - circRNA
KW - mRNA
KW - miRNA
UR - https://www.scopus.com/pages/publications/105010249957
U2 - 10.1186/s12888-025-07073-y
DO - 10.1186/s12888-025-07073-y
M3 - Artículo
C2 - 40634861
AN - SCOPUS:105010249957
SN - 1471-244X
VL - 25
JO - BMC Psychiatry
JF - BMC Psychiatry
IS - 1
M1 - 688
ER -