Hill, Matthew J.  ORCID: https://orcid.org/0000-0001-6776-8709, Donocik, Jacek G., Nuamah, Rosamond A., Mein, Charles A., Sainz-Fuertes, Ricardo and Bray, Nicholas J. ORCID: https://orcid.org/0000-0002-4357-574X
2014.
Transcriptional consequences of schizophrenia candidate miR-137 manipulation in human neural progenitor cells.
Schizophrenia Research
153
(1-3)
, pp. 225-230.
10.1016/j.schres.2014.01.034
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Abstract
MIR137, transcribed as the microRNA miR-137, is one of the leading candidate schizophrenia susceptibility genes to arise from large genome-wide association studies (GWAS) of the disorder. Recent data suggest that miR-137 modulates the expression of other schizophrenia susceptibility genes. Although bioinformatic resources are available with which to predict genes regulated by individual microRNA, there has been a lack of empirical data on genome-wide gene expression changes following miR-137 manipulation. We have therefore performed a genome-wide assessment of transcriptional changes in a human neural progenitor cell line after miR-137 over-expression and inhibition in order to elucidate molecular pathways by which genetic perturbation of miR-137 could promote susceptibility to schizophrenia. Bioinformatically-predicted miR-137 targets showed a small but highly significant down-regulation following miR-137 over-expression. Genes that were significantly down-regulated in association with miR-137 over-expression were enriched for involvement in neuronal differentiation. Differentially expressed genes that were confirmed by qPCR included others at genome-wide significant risk loci for schizophrenia (MAD1L1 and DPYD) and BDNF. These data point to molecular pathways through which genetic variation at the MIR137 locus could confer risk for schizophrenia.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Research Institutes & Centres > Neuroscience and Mental Health Research Institute (NMHII) Schools > Medicine Research Institutes & Centres > MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) |
| Subjects: | R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
| Uncontrolled Keywords: | Schizophrenia; GWAS; MicroRNA; miR-137; MIR137; Gene expression; Pathway |
| Publisher: | Elsevier |
| Funders: | MRC |
| Date of First Compliant Deposit: | 30 March 2016 |
| Date of Acceptance: | 24 January 2014 |
| Last Modified: | 05 May 2023 08:16 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/82231 |
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