@article{ref1,
title="Regulation of a truncated form of Tropomyosin-related kinase B (TrkB) by Hsa-miR-185* in frontal cortex of suicide completers",
journal="PLoS one",
year="2012",
author="Maussion, Gilles and Yang, Jennie and Yerko, Volodymyr and Barker, Philip and Mechawar, Naguib and Ernst, Carl and Turecki, Gustavo",
volume="7",
number="6",
pages="e39301-e39301",
abstract="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 (P(nominal): 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 = -0.439; p = 0.001). 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 22q11 region in psychopathology.<p /> <p>Language: en</p>",
language="en",
issn="1932-6203",
doi="10.1371/journal.pone.0039301",
url="http://dx.doi.org/10.1371/journal.pone.0039301"
}