Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers.

TitleRegulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers.
Publication TypeJournal Article
Year of Publication2014
AuthorsLopez JPablo, Fiori LM, Gross JA, Labonte B, Yerko V, Mechawar N, Turecki G
JournalInt J Neuropsychopharmacol
Volume17
Issue1
Pagination23-32
Date Published2014 Jan
ISSN1469-5111
Abstract

MicroRNAs (miRNAs) are small, non-coding RNA molecules that play an important role in the post-transcriptional regulation of mRNA. These molecules have been the subject of growing interest as they are believed to control the regulation of a large number of genes, including those expressed in the brain. Evidence suggests that miRNAs could be involved in the pathogenesis of neuropsychiatric disorders. Alterations in metabolic enzymes of the polyamine system have been reported to play a role in predisposition to suicidal behaviour. We have previously shown the expression of the polyamine genes SAT1 and SMOX to be down-regulated in the brains of suicide completers. In this study, we hypothesized that the dysregulation of these genes in depressed suicide completers could be influenced by miRNA post-transcriptional regulation. Using a stringent target prediction analysis, we identified several miRNAs that target the 3'UTR of SAT1 and SMOX. We profiled the expression of 10 miRNAs in the prefrontal cortex (BA44) of suicide completers (N = 15) and controls (N = 16) using qRT-PCR. We found that several miRNAs showed significant up-regulation in the prefrontal cortex of suicide completers compared to psychiatric healthy controls. Furthermore, we demonstrated a significant correlation between these miRNAs and the expression levels of both SAT1 and SMOX. Our results suggest a relationship between miRNAs and polyamine gene expression in the suicide brain, and postulate a mechanism for SAT1 and SMOX down-regulation by post-transcriptional activity of miRNAs.

DOI10.1017/S1461145713000941
Alternate JournalInt. J. Neuropsychopharmacol.
PubMed ID24025154
Grant List93775-1 / / Canadian Institutes of Health Research / Canada
93775-2 / / Canadian Institutes of Health Research / Canada
MOP 79253 / / Canadian Institutes of Health Research / Canada
119430-1 / / Canadian Institutes of Health Research / Canada
79253-1 / / Canadian Institutes of Health Research / Canada

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