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Non-coding RNA dysregulation in the amygdala region of schizophrenia patients contributes to the pathogenesis of the disease.

ABSTRACT: Schizophrenia (SCZ) is a neuropsychiatric disorder with a complex genetic etiology. The redundancy of the gene networks underlying SCZ indicates that many gene combinations have the potential to cause a system dysfunction that can manifest as SCZ or a related neurodevelopmental disorder. Recent studies show that small non-coding microRNA (miRNA) and long non-coding RNA (lncRNA) are important factors in shaping these networks and are dynamically regulated by neuronal activation. We investigated the genome-wide transcription profiles of 46 human amygdala samples obtained from 22 SCZ patients and 24 healthy controls. Using RNA sequencing (RNA-seq), we determined lncRNA expression levels in all samples and generated miRNA profiles for 27 individuals (13 cases and 14 controls). Previous studies have identified differentially expressed miRNAs in SCZ, including miR-132, miR-212, and miR-34a/miR-34c. Here we report differential expression of a novel miRNA, miR1307, in SCZ. Notably, miR1307 maps to a locus previously associated with SCZ through GWAS. Additionally, one lncRNA that was overexpressed in SCZ, AC005009.2, also maps to a region previously associated with SCZ based on GWAS and overlapped SCZ-related genes. The results were replicated in a large independent data set of 254 dorsolateral prefrontal cortex samples from the CommonMind consortium. Taken together, these results suggest that miRNA and lncRNAs are important contributors to the pathogenesis of SCZ.

SUBMITTER: Liu Y

PROVIDER: S-EPMC5804029 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Non-coding RNA dysregulation in the amygdala region of schizophrenia patients contributes to the pathogenesis of the disease.

Liu Yichuan Y Chang Xiao X Hahn Chang-Gyu CG Gur Raquel E RE Sleiman Patrick A M PAM Hakonarson Hakon H

Translational psychiatry 20180202 1

Schizophrenia (SCZ) is a neuropsychiatric disorder with a complex genetic etiology. The redundancy of the gene networks underlying SCZ indicates that many gene combinations have the potential to cause a system dysfunction that can manifest as SCZ or a related neurodevelopmental disorder. Recent studies show that small non-coding microRNA (miRNA) and long non-coding RNA (lncRNA) are important factors in shaping these networks and are dynamically regulated by neuronal activation. We investigated t ...[more]

PMID: 29391398

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Project description:Schizophrenia (SCZ) is a serious mental condition with an unknown cause. According to the reports, Brodmann Area 10 (BA10) is linked to the pathology and cortical dysfunction of SCZ, which demonstrates a number of replicated findings related to research on SCZ and the dysfunction in tasks requiring cognitive control in particular. Genetics' role in the pathophysiology of SCZ is still unclear. Therefore, it may be helpful to understand the effects of these changes on the onset and progression of SCZ to find novel mechanisms involved in the regulation of gene transcription. In order to determine the molecular regulatory mechanisms affecting the SCZ, the long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) axes in the BA10 area were determined using a bioinformatics approach in the present work. A microarray dataset (GSE17612) consisted of brain post-mortem tissues of the BA10 area from SCZ patients and matched healthy subjects was downloaded from the Gene Expression Omnibus (GEO) database. This dataset included probes for both lncRNAs and mRNAs. Using the R software's limma package, the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were found. The RNA interactions were also discovered using the DIANA-LncBase and miRTarBase databases. In the ceRNA network, positive correlations between DEmRNAs and DElncRNAs were evaluated using the Pearson correlation coefficient. Finally, lncRNA-associated ceRNA axes were built by using the co-expression and DElncRNA-miRNA-DEmRNA connections. We identified the DElncRNA-miRNA-DEmRNA axes, which included two key lncRNAs (PEG3-AS1, MIR570HG), seven key miRNAs (hsa-miR-124-3p, hsa-miR-17-5p, hsa-miR-181a-5p, hsa-miR-191-5p, hsa-miR-26a-5p, hsa-miR-29a-3p, hsa-miR-29b-3p), and eight key mRNAs (EGR1, ETV1, DUSP6, PLOD2, CD93, SERPINB9, ANGPTL4, TGFB2). Furthermore, DEmRNAs were found to be enriched in the "AGE-RAGE signaling pathway in diabetic complications", "Amoebiasis", "Transcriptional misregulation in cancer", "Human T-cell leukemia virus 1 infection", and "MAPK signaling pathway". This study offers research targets for examining significant molecular pathways connected to the pathogenesis of SCZ, even though the function of these ceRNA axes still needs to be investigated.

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Non-coding RNA dysregulation in the amygdala region of schizophrenia patients contributes to the pathogenesis of the disease.

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Non-coding RNA dysregulation in the amygdala region of schizophrenia patients contributes to the pathogenesis of the disease.

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