Ontology highlight
ABSTRACT:
PROVIDER: PRJNA721832 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2012-06-02 | GSE34120 | GEO
Project description:Stage T1 bladder cancers have the highest progression and recurrence rates of all non-muscle invasive bladder tumors. T1 tumors are heterogeneous; while most T1 patients are treated with BCG, many will progress and die from bladder cancer, and particularly aggressive tumors could be treated by early cystectomy. To better understand the molecular heterogeneity of T1 cancers, we performed transcriptome profiling and unsupervised clustering, identifying five consensus subtypes of T1 tumors treated with reTUR, induction and maintenance BCG. The T1-LumGU subtype was associated with CIS (6/13, 46% of all CIS), had high E2F1 and EZH2 expression, and enriched E2F target and G2M checkpoint Hallmarks. T1-Inflam was inflamed and infiltrated with immune cells. While most T1 tumors were classified as luminal papillary, the T1-TLum subtype had the highest median Luminal Papillary score and FGFR3 expression, no recurrence events, and the fewest copy number gains. T1-Myc and T1-Early subtypes had the most recurrences (14/30 within 24 months), highest median MYC expression, and, when combined, had significantly worse recurrence-free survival than the other three subtypes. T1-Early had 5 (38%) recurrences within the first 6 months of BCG, and repressed IFN-alpha and IFN-gamma Hallmarks and inflammation. We developed a single-patient T1 classifier and validated our subtype biology in a second cohort of T1 tumors. Future research will be necessary to validate the proposed T1 subtypes and to determine if therapies can be individualized for each subtype.
2020-07-13 | GSE154261 | GEO