regulation of a truncated form of tropomyosin-related kinase b (trkb) by hsa-mir-185 in frontal cortex of suicide completers规定一种截断tropomyosin-related激酶b(trkb)hsa - mir - 185自杀死亡者的额叶皮质.pdfVIP

Regulation of a Truncated Form of Tropomyosin-Related Kinase B (TrkB) by Hsa-miR-185* in Frontal Cortex of Suicide Completers 1 1 1 2 1 1 Gilles Maussion , Jennie Yang , Volodymyr Yerko , Philip Barker , Naguib Mechawar , Carl Ernst , Gustavo Turecki1* 1 McGill Group for Suicide Studies, Douglas Hospital Research Institute, McGill University, Montreal, Quebec, Canada, 2 Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada 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 (Pnominal: 9.1025 and 1.8.1024 respectively; FDR-corrected p = 0.031). Bioinformatic analyses revealed five putative binding sites for the DiGeorge syndrome linked microRNA Hsa-miR-185*in the 39UTR of TrkB-T1, but none for Hsa-miR-491- 3P. The increase of Hsa-miR-185* in frontal cortex of suicide completers was valida