Dysregulation of circRNA expression in the peripheral blood of individuals with schizophrenia and bipolar disorder

Springer Science and Business Media LLC - Tập 99 - Trang 981-991 - 2021
Ebrahim Mahmoudi1,2,3, Melissa J. Green4,5, Murray J. Cairns1,2,3
1School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia
2Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, Australia
3Hunter Medical Research Institute, New Lambton Heights, Australia
4School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia
5Neuroscience Research Australia (NeuRA), Randwick, Australia

Tóm tắt

Circular RNAs (circRNAs) are head-to-tail back-spliced RNA transcripts that have been linked to several biological processes and their perturbation is evident in human disease, including neurological disorders. There is also emerging research suggesting circRNA expression may also be altered in psychiatric and behavioural syndromes. Here, we provide a comprehensive analysis of circRNA expression in peripheral blood mononuclear cells (PBMCs) from 39 patients with schizophrenia and bipolar disorder as well as 20 healthy individuals using deep RNA-seq. We observed systematic alternative splicing leading to a complex and diverse profile of RNA transcripts including 8762 high confidence circRNAs. More specific scrutiny of the circular transcriptome in schizophrenia and bipolar disorder, compared to a non-psychiatric control group, revealed significant dysregulation of 55 circRNAs with a bias towards downregulation. These molecules were predicted to interact with a large number of miRNAs that target genes enriched in psychiatric disorders. Further replication and cross-validation to determine the specificity of these circRNAs across broader diagnostic groups and subgroups in psychiatry will enable their potential utility as biomarkers to be established. • We identified 8762 high confidence circRNAs with systematic alternative splicing in human PBMCs. • CircRNAs were dysregulated in schizophrenia and bipolar disorder, compared to a non-psychiatric control group. • The DE circRNAs were predicted to interact with miRNAs with target genes enriched in psychiatric disorders. • Some circRNAs have the potential to serve as biomarkers in psychiatry.

Tài liệu tham khảo

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