Non-Coding RNA as Novel Players in the Pathophysiology of Schizophrenia

Gibbons, Andrew S.; Udawela, Madhara; Dean, Brian

doi:10.3390/ncrna4020011

Cited by 47 publications

(30 citation statements)

References 159 publications

(195 reference statements)

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“…Over the past decade, dysregulated processing and altered abundance of a wide range of miRNAs have been associated with neurodegenerative disorders [5] and neuroblastoma [6]. Widespread changes in miRNA levels have also been observed in developmental brain disorders (DBDs) including autism spectrum disorders (ASD) [7], schizophrenia [8], intellectual disability (ID) [9], and epilepsy [10]. However, the precise miRNA-based mechanisms during brain development and in higher-order brain processing, including learning and memory and cognition, are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Loss of the neurodevelopmental disease-associated gene miR-146a impairs neural progenitor differentiation and causes learning and memory deficits

et al. 2020

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Background: Formation and maintenance of appropriate neural networks require tight regulation of neural stem cell proliferation, differentiation, and neurogenesis. microRNAs (miRNAs) play an important role in brain development and plasticity, and dysregulated miRNA profiles have been linked to neurodevelopmental disorders including autism, schizophrenia, or intellectual disability. Yet, the functional role of miRNAs in neural development and postnatal brain functions remains unclear. Methods: Using a combination of cell biology techniques as well as behavioral studies and brain imaging, we characterize mouse models with either constitutive inactivation or selectively hippocampal knockdown of the neurodevelopmental disease-associated gene Mir146a, the most commonly deregulated miRNA in developmental brain disorders (DBD). Results: We first show that during development, loss of miR-146a impairs the differentiation of radial glial cells, neurogenesis process, and neurite extension. In the mouse adult brain, loss of miR-146a correlates with an increased hippocampal asymmetry coupled with defects in spatial learning and memory performances. Moreover, selective hippocampal downregulation of miR-146a in adult mice causes severe hippocampal-dependent memory impairments indicating for the first time a role for this miRNA in postnatal brain functions. Conclusion: Our results show that miR-146a expression is critical for correct differentiation of neural stem cell during brain development and provide for the first time a strong argument for a postnatal role of miR-146a in regulating hippocampal-dependent memory. Furthermore, the demonstration that the Mir146a −/− mouse recapitulates several aspects reported in DBD patients, including impaired neurogenesis, abnormal brain anatomy, and working and spatial memories deficits, provides convincing evidence that the dysregulation of miR146a contributes to the pathogenesis of DBDs.

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Section: Introductionmentioning

confidence: 99%

Loss of the neurodevelopmental disease-associated gene miR-146a impairs neural progenitor differentiation and causes learning and memory deficits

et al. 2020

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“…These regulatory short ncRNAs are believed to manage expression of 20 to 60 percent of protein-coding genes in mammalian genomes [ 116 , 117 , 118 ]. At the same time, the dysregulation of miRNA expression can cause a number of psychiatric disorders, including SZ [ 12 ]. For a long time, miRNAs have been considered to be potential therapeutic agents themselves [ 119 ].…”

Section: Concluding Remarks: Perspectives Of Circular Rnas Therapymentioning

confidence: 99%

“…Genome-wide association studies (GWASs) have described only approximately 200 genome SNPs’ susceptibility loci for SZ [ 11 ]. Recent studies have shown that gene expression dysregulation, which is triggered by a number of epigenetic factors and aberrant expression of non-coding RNAs, could be one of the key causes of SZ and other psychiatric disorders [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

The Biomarker and Therapeutic Potential of Circular Rnas in Schizophrenia

Nedoluzhko

Gruzdeva

Sharko

et al. 2020

Cells

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Circular RNAs (circRNAs) are endogenous, single-stranded, most frequently non-coding RNA (ncRNA) molecules that play a significant role in gene expression regulation. Circular RNAs can affect microRNA functionality, interact with RNA-binding proteins (RBPs), translate proteins by themselves, and directly or indirectly modulate gene expression during different cellular processes. The affected expression of circRNAs, as well as their targets, can trigger a cascade of events in the genetic regulatory network causing pathological conditions. Recent studies have shown that altered circular RNA expression patterns could be used as biomarkers in psychiatric diseases, including schizophrenia (SZ); moreover, circular RNAs together with other cell molecules could provide new insight into mechanisms of this disorder. In this review, we focus on the role of circular RNAs in the pathogenesis of SZ and analyze their biomarker and therapeutic potential in this disorder.

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“…LncRNAs in the cytoplasm function as competing endogenous RNAs (ceRNAs) acting as molecular sponges for miRNAs, targeting proteins to regulate their expression, and suppressing translation by targeting mRNAs [13]. In addition to their various roles in cells, lncRNAs are also involved in various human diseases including cardiovascular diseases, autoimmune diseases, neurodegenerative disorders, and psychiatric disorders [10, 14, 15]. In particular, lncRNAs are reported to be closely associated with tumorigenesis [8].…”

Section: Long Non-coding Rnasmentioning

confidence: 99%

Roles of Oncogenic Long Non-coding RNAs in Cancer Development

Kim

2018

Genomics Inform

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Long non-coding RNAs (lncRNAs) are classified as RNAs that are longer than 200 nucleotides and cannot be translated into protein. Several studies have demonstrated that lncRNAs are directly or indirectly involved in a variety of biological processes and in the regulation of gene expression. In addition, lncRNAs have important roles in many diseases including cancer. It has been shown that abnormal expression of lncRNAs is observed in several human solid tumors. Several studies have shown that many lncRNAs can function as oncogenes in cancer development through the induction of cell cycle progression, cell proliferation and invasion, anti-apoptosis, and metastasis. Oncogenic lncRNAs have the potential to become promising biomarkers and might be potent prognostic targets in cancer therapy. However, the biological and molecular mechanisms of lncRNA involvement in tumorigenesis have not yet been fully elucidated. This review summarizes studies on the regulatory and functional roles of oncogenic lncRNAs in the development and progression of various types of cancer.

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Non-Coding RNA as Novel Players in the Pathophysiology of Schizophrenia

Cited by 47 publications

References 159 publications

Loss of the neurodevelopmental disease-associated gene miR-146a impairs neural progenitor differentiation and causes learning and memory deficits

Loss of the neurodevelopmental disease-associated gene miR-146a impairs neural progenitor differentiation and causes learning and memory deficits

The Biomarker and Therapeutic Potential of Circular Rnas in Schizophrenia

Roles of Oncogenic Long Non-coding RNAs in Cancer Development

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