Dataset Information

Temporal dynamics of miRNAs in human DLPFC and its association with miRNA dysregulation in schizophrenia.

ABSTRACT: Brain development is dependent on programmed gene expression, which is both genetically and epigenetically regulated. Post-transcriptional regulation of gene expression by microRNAs (miRNAs) is essential for brain development. As abnormal brain development is hypothesized to be associated with schizophrenia, miRNAs are an intriguing target for this disorder. The aims of this study were to determine the temporal dynamics of miRNA expression in the human dorsolateral prefrontal cortex (DLPFC), and the relationship between miRNA's temporal expression pattern and dysregulation in schizophrenia. This study used next-generation sequencing to characterize the temporal dynamics of miRNA expression in the DLPFC of 109 normal subjects (second trimester-74 years of age) and miRNA expression changes in 34 schizophrenia patients. Unlike mRNAs, the majority of which exhibits a wave of change in fetuses, most miRNAs are preferentially expressed during a certain period before puberty. It is noted that in schizophrenia patients, miRNAs normally enriched in infants tend to be upregulated, while those normally enriched in prepuberty tend to be downregulated, and the targets of these miRNAs are enriched for genes encoding synaptic proteins and those associated with schizophrenia. In addition, miR-936 and miR-3162 were found to be increased in the DLPFC of patients with schizophrenia. These findings reveal the temporal dynamics of miRNAs in the human DLPFC, implicate the importance of miRNAs in DLPFC development, and suggest a possible link between schizophrenia and dysregulation of miRNAs enriched in infancy and prepuberty.

SUBMITTER: Hu Z

PROVIDER: S-EPMC6702224 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Temporal dynamics of miRNAs in human DLPFC and its association with miRNA dysregulation in schizophrenia.

Hu Zhonghua Z Gao Shouguo S Lindberg Daniel D Panja Debabrata D Wakabayashi Yoshi Y Li Keshen K Kleinman Joel E JE Zhu Jun J Li Zheng Z

Translational psychiatry 20190820 1

Brain development is dependent on programmed gene expression, which is both genetically and epigenetically regulated. Post-transcriptional regulation of gene expression by microRNAs (miRNAs) is essential for brain development. As abnormal brain development is hypothesized to be associated with schizophrenia, miRNAs are an intriguing target for this disorder. The aims of this study were to determine the temporal dynamics of miRNA expression in the human dorsolateral prefrontal cortex (DLPFC), and ...[more]

PMID: 31431609

Similar Datasets

Project description:Little is known about the molecular pathogenesis of schizophrenia, possibly because of unrecognized heterogeneity in diagnosed patient populations. We analyzed gene expression data collected from the dorsolateral prefrontal cortex (DLPFC) of post-mortem frozen brains of 189 adult diagnosed schizophrenics and 206 matched controls. Transcripts from 633 genes are differentially expressed in the DLPFC of schizophrenics as compared to controls at Bonferroni-corrected significance levels. Seventeen of those genes are differentially expressed at very high significance levels (<10-8 after Bonferroni correction). The findings were closely replicated in a dataset from an entirely unrelated source. The statistical significance of this differential gene expression is being driven by about half of the schizophrenic DLPFC samples, and importantly, it is the same half of the samples that is driving the significance for almost all of the differentially expressed transcripts. Weighted gene co-expression network analysis (WGCNA) of the schizophrenic subjects, based on the transcripts differentially expressed in the schizophrenics as compared to controls, divides them into two groups. "Type 1" schizophrenics have a DLPFC transcriptome similar to that of controls with only four differentially expressed genes identified. "Type 2" schizophrenics have a DLPFC transcriptome dramatically different from that of controls, with 3529 expression array probes to 3092 genes detecting transcripts that are differentially expressed at very high significance levels. These findings were re-tested and replicated in a separate independent cohort, using the RNAseq data from the DLPFC of an independent set of schizophrenics and control subjects. We suggest the hypothesis that these striking differences in DLPFC transcriptomes, identified and replicated in two populations, imply a fundamental biologic difference between these two groups of diagnosed schizophrenics, and we propose specific paths for further testing and expanding the hypothesis.

Dataset Information

Temporal dynamics of miRNAs in human DLPFC and its association with miRNA dysregulation in schizophrenia.

Publications

Temporal dynamics of miRNAs in human DLPFC and its association with miRNA dysregulation in schizophrenia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets