title: Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers.
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.
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, H4H 1R3, Canada.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Lopez
authors.forename: Laura M
authors.initials: LM
authors.lastname: Fiori
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Gross
authors.forename: Benoit
authors.initials: B
authors.lastname: Labonte
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Yerko
authors.forename: Naguib
authors.initials: N
authors.lastname: Mechawar
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
mesh_terms: D000123:Acetyltransferases / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D003863:Depression / Q000235:genetics* / Q000523:psychology; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011073:Polyamines / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D013405:Suicide / Q000523:psychology*; D055815:Young Adult; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D035683:MicroRNAs; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase