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| Status |
Public on Jun 02, 2012 |
| Title |
Differential microRNA profile in frontal cortex of suicide completers compared to control |
| Platform organisms |
Homo sapiens; Mus musculus; Rattus norvegicus; Human alphaherpesvirus 1; Human betaherpesvirus 5; Murid betaherpesvirus 1; human gammaherpesvirus 4; JC polyomavirus; Human immunodeficiency virus 1; Murid gammaherpesvirus 4; Human gammaherpesvirus 8; Betapolyomavirus hominis; Betapolyomavirus macacae |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Background:
TrkB-T1 is a BDNF receptor lacking a tyrosine kinase domain that is highly expressed in astrocytes and regulates BDNF-evoked calcium transients. Previous studies indicate that downregulation of TrkB-T1 in frontal cortex may be involved in neurobiological processes underlying suicide.
Methods:
In a microarray screening study (N=8), we interrogated all known microRNA in the frontal cortex of suicide completers with low expression of TrkB-T1 and normal controls. These findings were validated and followed up in a larger sample of cases and controls (N=55) Functional analyses included microRNA silencing, microRNA overexpression and luciferase assays to investigate specificity and to validate interactions between differentially expressed microRNA and TrkB-T1
Results:
microRNAs Hsa-miR-185* and Hsa-miR-491-3p were upregulated in suicide completers with low expression of TrkB.T1 (Pnominal: 9.10-5 and 1.8.10-4 respectively; FDR-corrected p=0.031). Bioinformatic analyses revealed five putative binding sites for the DiGeorge syndrome linked microRNA Hsa-miR-185*in the 3’UTR of TrkB-T1, but none for Hsa-miR-491-3P. The increase of Hsa-miR-185* in frontal cortex of suicide completers was validated then confirmed in a larger, randomly selected group of suicide completers, where an inverse correlation between Hsa-miR-185* and TrkB-T1 expression was observed ( R=-0.404; p=0.002). Silencing and overexpression studies performed in human cell lines confirmed the inverse relationship between hsa-mir-185* and trkB-T1 expression. Luciferase assays demonstrated that Hsa-miR-185* binds to sequences in the 3’UTR of TrkB-T1.
Conclusion:
These results suggest that an increase of Hsa-miR-185* expression levels regulates, at least in part, the TrkB-T1 decrease observed in the frontal cortex of suicide completers and further implicate the 3MB 22q11 region in psychopathology.
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| Overall design |
The microarray analysis consists in to compare the microRNA profile of four suicide completers with low TrkB-T1 expression level and four controls.
Each RNA extract was labeled with Hy3 and hybridyzed with a reference sample labeled with Hy5. The reference sample was a pool of the eight RNA samples
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| Contributor(s) |
Maussion G, Yang J, Yerko V, Barker P, Mechawar N, Ernst C, Turecki G |
| Citation(s) |
22802923 |
| |
| Submission date |
Dec 02, 2011 |
| Last update date |
Jan 13, 2016 |
| Contact name |
Gilles Maussion |
| Organization name |
INSERM U675
|
| Street address |
16 rue Henri Huchard
|
| City |
PARIS |
| ZIP/Postal code |
75018 |
| Country |
France |
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| Platforms (1) |
| GPL7722 |
miRCURY LNA microRNA Array, v.10.0 - hsa, mmu & rno |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA149873 |
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