Upregulation of dicer and microRNA expression in the dorsolateral prefrontal cortex Brodmann area 46 in schizophrenia.
BACKGROUND
MicroRNA (miRNA) are capable of regulating multitudes of target genes and are essential factors in mediating healthy neurodevelopment. We hypothesize that abnormal miRNA levels contribute to the complex global changes in gene expression that underlie the pathophysiology of schizophrenia.


METHODS
With a commercial bead array platform, we investigated miRNA expression in 74 samples of postmortem dorsolateral prefrontal cortex (Brodmann Area 46) (n = 37 matched pairs schizophrenia/schizoaffective disorder and control subjects). A subset of differentially expressed miRNA and genes in the miRNA biogenesis pathway was also analyzed with quantitative reverse transcription-polymerase chain reaction. Gene targets of miRNAs demonstrating significantly altered expression were predicted, and pathways analysis was performed.


RESULTS
After correction for multiple testing, microarray analysis identified differential expression of 28 miRNA in the schizophrenia group. Significantly, 89% of these molecules were elevated in accordance with earlier work in other brain regions that showed a broad increase in miRNA expression in schizophrenia. These observations were supported by quantitative reverse transcription-polymerase chain reaction, for miR-328, miR-17-5p, miR-134, miR-652, miR-382, and miR-107 and were consistent with a schizophrenia-associated increase in miRNA processing through elevated Dicer expression. Target and pathways analysis provided insight into the potential cellular effects, with particular enrichment of miRNA targets in axon guidance and long-term potentiation.


CONCLUSIONS
These results suggest that schizophrenia is associated with altered miRNA biogenesis and expression, which might have important implications in the complex pathophysiology of the disorder.
Schizophrenia Research Institute, Sydney, Australia.
Danielle M
DM
Santarelli
Natalie J
NJ
Beveridge
Paul A
PA
Tooney
Murray J
MJ
Cairns
D016022:Case-Control Studies; D020869:Gene Expression Profiling; D006801:Humans; D016555:Matched-Pair Analysis; D035683:MicroRNAs / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D011618:Psychotic Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012016:Reference Values; D012260:Ribonucleases / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation
D035683:MicroRNAs; D012260:Ribonucleases