Transcriptional consequences of schizophrenia candidate miR-137 manipulation in human neural progenitor cells

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:	Neuroscience and Mental Health Research Institute (NMHRI) Medicine 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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