Whole transcriptome sequencing to uncover CircRNA expression patterns linked to schizophrenia pathogenesis

Area of Science:

• Genomics
• Molecular Biology
• Psychiatry

Background:

• Schizophrenia (SCZ) pathogenesis is complex, lacking objective diagnostic indicators.
• Whole-transcriptome analysis offers potential for early diagnostic marker discovery.
• The role of circular RNAs (circRNAs) in SCZ remains largely unexplored.

Purpose of the Study:

• To investigate differentially expressed circRNAs in the peripheral blood of SCZ patients.
• To identify potential circRNA-based diagnostic markers for SCZ.
• To explore the regulatory networks involving circRNAs in SCZ.

Main Methods:

• Whole transcriptome analysis of peripheral blood from 5 SCZ patients and 5 controls.
• Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
• Prediction of competing endogenous RNA (ceRNA) networks, protein-protein interactions, and circRNA-RNA binding protein (RBP) interactions.
• Quantitative real-time PCR (qRT-PCR) for circRNA expression validation.

Main Results:

• Profiled 38,699 circRNAs, identifying 589 differentially expressed circRNAs (DEcircRNAs).
• Host genes of DEcircRNAs are implicated in TNF and Wnt signaling pathways.
• Constructed a ceRNA network; identified three significantly upregulated DEcircRNAs (hsa_circ_0006157, hsa_circ_0071422, hsa_circ_0071095) in SCZ patients.
• Identified 27 RBPs binding to DEcircRNAs, including significantly expressed DDX54 and RBM15B.

Conclusions:

• Upregulated circRNAs hsa_circ_0006157, hsa_circ_0071422, and hsa_circ_0071095 show promise as potential diagnostic markers for SCZ.
• Further functional studies are required to confirm the precise role of these circRNAs in SCZ pathogenesis.