MicroRNAs suggest a new mechanism for altered brain gene expression in schizophrenia

Coyle, Joseph T.

doi:10.1073/pnas.0813321106

Cited by 27 publications

(8 citation statements)

References 16 publications

(12 reference statements)

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“…The results of correlation between clinical symptoms and miRNA expression levels suggest that lymphocyte could reflect the metabolism of brain cells, and may be exploited as a neural and possible genetic probe in studies of psychiatric disorders [15] – [16] . Since a specific miRNA might be involved in coordinated regulation of protein expression in functional networks [24] , this kind of biomarkers might contribute to new development of target therapeutic intervention in near future [8] . We conclude that genome-wide miRNA profiling is a feasible way to identify potential biomarkers for schizophrenia, and the seven-miRNA signature warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Expression Aberration as Potential Peripheral Blood Biomarkers for Schizophrenia

et al. 2011

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Since brain tissue is not readily accessible, a new focus in search of biomarkers for schizophrenia is blood-based expression profiling of non-protein coding genes such as microRNAs (miRNAs), which regulate gene expression by inhibiting the translation of messenger RNAs. This study aimed to identify potential miRNA signature for schizophrenia by comparing genome-wide miRNA expression profiles in patients with schizophrenia vs. healthy controls. A genome-wide miRNA expression profiling was performed using a Taqman array of 365 human miRNAs in the mononuclear leukocytes of a learning set of 30 cases and 30 controls. The discriminating performance of potential biomarkers was validated in an independent testing set of 60 cases and 30 controls. The expression levels of the miRNA signature were then evaluated for their correlation with the patients' clinical symptoms, neurocognitive performances, and neurophysiological functions. A seven-miRNA signature (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652) was derived from a supervised classification with internal cross-validation, with an area under the curve (AUC) of receiver operating characteristics of 93%. The putative signature was then validated in the testing set, with an AUC of 85%. Among these miRNAs, miR-34a was differentially expressed between cases and controls in both the learning (P = 0.005) and the testing set (P = 0.002). These miRNAs were differentially correlated with patients' negative symptoms, neurocognitive performance scores, and event-related potentials. The results indicated that the mononuclear leukocyte-based miRNA profiling is a feasible way to identify biomarkers for schizophrenia, and the seven-miRNA signature warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

MicroRNA Expression Aberration as Potential Peripheral Blood Biomarkers for Schizophrenia

et al. 2011

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“…The translation of mRNA to protein is regulated by mechanisms that control 5Ј capping, 3Ј polyadenylation, splicing, RNA editing, mRNA transport, stability, and initiation and elongation ( VanDongen and VanDongen, 2004;Coyle, 2009). The 5Ј-UTR of most glutamate receptor mRNAs is unusually long.…”

Section: Translational Control Of Glutamate Receptorsmentioning

confidence: 99%

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

et al. 2010

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“…It has also been reported that miRNA hsa-miR-195 regulates BDNF and alters the expression of downstream GABAergic transcripts in schizophrenia [ 10 ]. Most recently, studies found that a miRNA regulates signaling downstream from the NMDA receptor, suggesting miRNAs as a new mechanism for altering brain gene expression in schizophrenia [ 11 , 12 ]. This accumulating data suggests that miRNAs may play important roles in the expression of genes linked to schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

A Novel microRNA and transcription factor mediated regulatory network in schizophrenia

et al. 2010

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BackgroundSchizophrenia is a complex brain disorder with molecular mechanisms that have yet to be elucidated. Previous studies have suggested that changes in gene expression may play an important role in the etiology of schizophrenia, and that microRNAs (miRNAs) and transcription factors (TFs) are primary regulators of this gene expression. So far, several miRNA-TF mediated regulatory modules have been verified. We hypothesized that miRNAs and TFs might play combinatory regulatory roles for schizophrenia genes and, thus, explored miRNA-TF regulatory networks in schizophrenia.ResultsWe identified 32 feed-forward loops (FFLs) among our compiled schizophrenia-related miRNAs, TFs and genes. Our evaluation revealed that these observed FFLs were significantly enriched in schizophrenia genes. By converging the FFLs and mutual feedback loops, we constructed a novel miRNA-TF regulatory network for schizophrenia. Our analysis revealed EGR3 and hsa-miR-195 were core regulators in this regulatory network. We next proposed a model highlighting EGR3 and miRNAs involved in signaling pathways and regulatory networks in the nervous system. Finally, we suggested several single nucleotide polymorphisms (SNPs) located on miRNAs, their target sites, and TFBSs, which may have an effect in schizophrenia gene regulation.ConclusionsThis study provides many insights on the regulatory mechanisms of genes involved in schizophrenia. It represents the first investigation of a miRNA-TF regulatory network for a complex disease, as demonstrated in schizophrenia.

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MicroRNAs suggest a new mechanism for altered brain gene expression in schizophrenia

Cited by 27 publications

References 16 publications

MicroRNA Expression Aberration as Potential Peripheral Blood Biomarkers for Schizophrenia

MicroRNA Expression Aberration as Potential Peripheral Blood Biomarkers for Schizophrenia

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

A Novel microRNA and transcription factor mediated regulatory network in schizophrenia

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