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.
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MiRNA expression levels were also found to be altered in BA10, BA44, anterior cingulate cortex, and other brain regions in MDD.
“MiRNA expression levels were also found to be altered in BA10,244 BA44,245 anterior cingulate cortex (ACC),246 and other brain regions in MDD.247”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [245]
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- Authors
- Lopez, J. P., Fiori, L. M., Gross, J. A., Labonte, B., Yerko, V., Mechawar, N., & Turecki, G.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Turecki, Gustavo
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-09-12
- Volume
- 17
- Issue
- 01
- Pages
- 23-32
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2162158370
- Cited by
- 103
- References
- 8
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 8 · 2022: 9 · 2021: 12 · 2020: 10 · 2019: 7 · 2018: 13 · 2017: 11 · 2016: 10 · 2015: 7 · 2014: 8 · 2013: 2
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Faculty of Medicine, McGill University
- Canadian Institutes of Health Research (93775_2, 79253_1, 93775_1, MOP 79,253, 119430_1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Keywords
- microRNA, polyamine metabolism, SAT1, SMOX, prefrontal cortex, suicide, depression, post-transcriptional regulation, miRNA expression profiling, suicidal behavior
- MeSH terms
- Polyamine Oxidase, Diamine N-Acetyltransferase, Acetyltransferases, Adult, Oxidoreductases Acting on CH-NH Group Donors, Depression, Gene Expression Regulation, Humans, Male, Polyamines, Suicide, Case-Control Studies, Prefrontal Cortex, MicroRNAs, Young Adult
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