Schizophrenia-associated MicroRNA-GeneInteractions in the Dorsolateral Prefrontal Cortex
- Author:
Santarelli M. DANIELLE
1
;
Carroll P. ADAM
;
Cairns M. HEATH
;
Tooney A. PAUL
;
Cairns J. MURRAY
Author Information
1. School of Biomedical Sciences and Pharmacy
- Keywords:
Schizophrenia;
MicroRNA;
Dorsolateral prefrontal cor-tex;
Network;
Neuropathology
- From:
Genomics, Proteomics & Bioinformatics
2019;17(6):623-634
- CountryChina
- Language:Chinese
-
Abstract:
Schizophrenia-associated anomalies in gene expression in postmortem brain can be attributed to a combination of genetic and environmental influences. Given the small effect size of common variants, it is likely that we may only see the combined impact of some of these at the pathway level in small postmortem studies. At the gene level, however, there may be more impact from common environmental exposures mediated by influential epigenomic modifiers, such as microRNA (miRNA). We hypothesise that dysregulation of miRNAs and their alteration of gene expression have significant implications in the pathophysiology of schizophrenia. In this study, we integrate changes in cortical gene and miRNA expression to identify regulatory interactions and networks associated with the disorder. Gene expression analysis in post-mortem prefrontal dorso-lateral cortex (BA 46) (n=74 matched pairs of schizophrenia, schizoaffective, and control samples) was integrated with miRNA expression in the same cohort to identify gene-miRNA regulatory net-works. A significant gene-miRNA interaction network was identified, including miR-92a, miR-495, and miR-134, which converged with differentially expressed genes in pathways involved in neurode-velopment and oligodendrocyte function. The capacity for miRNA to directly regulate gene expres-sion through respective binding sites in BCL11A, PLP1, and SYT11 was also confirmed to support the biological relevance of this integrated network model. The observations in this study support thehypothesis that miRNA dysregulation is an important factor in the complex pathophysiology of schizophrenia.
