An introduction to microRNAs and their dysregulation in psychiatric disorders

Chao, Yu-Lin; Chen, Chia‐Hsiang

doi:10.1016/j.tcmj.2012.12.003

Cited by 10 publications

(10 citation statements)

References 77 publications

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“…Six miRNAs miR-137, miR-148a-3p, miR-338-3p, miR-30a/b-5p and miR-22-3p known to be associated with several cancers were chosen to study the expression levels in oral tumors 20 , 25 , 26 . Interestingly, all these miRNAs were also reported to be dysregulated in neuronal development and psychiatric disorders 19 , 27 .…”

Section: Discussionmentioning

confidence: 99%

LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors

Arunkumar

Anand

Raksha

et al. 2018

Sci Rep

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Long non-coding RNAs (lncRNAs) play an important role in the regulation of key cellular processes in early development and cancer. LncRNA Oip5-as1 facilitates stem cell self-renewal in mouse by sponging mmu-miR-7 and modulating NANOG level, yet its role in cancer is less understood. We analyzed OIP5-AS1 expression in oral tumors and in TCGA datasets. We observed overexpression of OIP5-AS1 in oral tumors (P < 0.001) and in tumors of epithelial origin from TCGA. OIP5-AS1 expression was strongly associated with undifferentiated tumors (P = 0.0038). In silico analysis showed miR-7 binding site is conserved in mouse and human OIP5-AS1. However, human NANOG 3′-UTR lost the binding site for hsa-miR-7a-3. Therefore, we screened for other miRNAs that can be sponged by OIP5-AS1 and identified six potential miRNAs and their downstream target genes. Expression analysis showed downregulation of miRNAs and upregulation of downstream target genes, particularly in undifferentiated tumors with high-level of OIP5-AS1 suggesting OIP5-AS1 could post-transcriptionally modulate the downstream target genes. Further, systematic epigenomic analysis of OIP5-AS1 promoter revealed binding motifs for MYC, NANOG and KLF4 suggesting that OIP5-AS1 could be transactivated by stemness-associated transcription factors in cancer. OIP5-AS1 overexpression in undifferentiated oral tumors may be suggestive of enhanced cancer stemness, and consequently, poor clinical outcome.

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Section: Discussionmentioning

confidence: 99%

LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors

Arunkumar

Anand

Raksha

et al. 2018

Sci Rep

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“…Accumulating evidence implicates miRNAs with schizophrenia: miRNAs are known to play important roles in brain development 4 ; miRNAs are found differentially expressed in postmortem brains of patients with schizophrenia 5 ; and miRNAs and their targets are found enriched in risk loci from genetic studies at the level of copy number variations (CNVs) as well as common and rare variations. [6][7][8][9] Additionally, much of the signal in genome-wide association studies (GWASs) of schizophrenia is believed to come from variants altering gene expression, 10,11 thus putting miRNAs as regulators of gene expression into the spotlight.…”

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confidence: 99%

Analyzing the Role of MicroRNAs in Schizophrenia in the Context of Common Genetic Risk Variants

et al. 2016

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; for the Schizophrenia Working Group of the Psychiatric Genomics Consortium IMPORTANCE The recent implication of 108 genomic loci in schizophrenia marked a great advancement in our understanding of the disease. Against the background of its polygenic nature there is a necessity to identify how schizophrenia risk genes interplay. As regulators of gene expression, microRNAs (miRNAs) have repeatedly been implicated in schizophrenia etiology. It is therefore of interest to establish their role in the regulation of schizophrenia risk genes in disease-relevant biological processes. OBJECTIVE To examine the role of miRNAs in schizophrenia in the context of disease-associated genetic variation. DESIGN, SETTING, AND PARTICIPANTS The basis of this study was summary statistics from the largest schizophrenia genome-wide association study meta-analysis to date (83 550 individuals in a meta-analysis of 52 genome-wide association studies) completed in 2014 along with publicly available data for predicted miRNA targets. We examined whether schizophrenia risk genes were more likely to be regulated by miRNA. Further, we used gene set analyses to identify miRNAs that are regulators of schizophrenia risk genes. MAIN OUTCOMES AND MEASURES Results from association tests for miRNA targetomes and related analyses. RESULTS In line with previous studies, we found that similar to other complex traits, schizophrenia risk genes were more likely to be regulated by miRNAs (P < 2 × 10 −16). Further, the gene set analyses revealed several miRNAs regulating schizophrenia risk genes, with the strongest enrichment for targets of miR-9-5p (P = .0056 for enrichment among the top 1% most-associated single-nucleotide polymorphisms, corrected for multiple testing). It is further of note that MIR9-2 is located in a genomic region showing strong evidence for association with schizophrenia (P = 7.1 × 10 −8). The second and third strongest gene set signals were seen for the targets of miR-485-5p and miR-137, respectively. CONCLUSIONS AND RELEVANCE This study provides evidence for a role of miR-9-5p in the etiology of schizophrenia. Its implication is of particular interest as the functions of this neurodevelopmental miRNA tie in with established disease biology: it has a regulatory loop with the fragile X mental retardation homologue FXR1 and regulates dopamine D 2 receptor density.

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“…This discrepancy could be resulting from the fact that the duration of drug treatment was only 24 h in our study whereas, Zhou et al (2009) treated the rats for four weeks. In post-mortem brains of schizophrenic patients and anti-depressant-treated subjects with major depressive disorder, miR-128 has been shown to have increased expression (Bocchio-Chiavetto et al, 2013; Chao and Chen, 2013; Dwivedi, 2014). Moreover, in rats treated with an antipsychotic drug, haloperidol, miR-128 expression was found to be increased, however this effect was not extendable to human schizophrenic patients in the study (Perkins et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Drugs used to treat bipolar disorder act via microRNAs to regulate expression of genes involved in neurite outgrowth

et al. 2020

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Background: The drugs commonly used to treat bipolar disorder have limited efficacy and drug discovery is hampered by the paucity of knowledge of the pathophysiology of this disease. This study aims to explore the role of microRNAs in bipolar disorder and understand the molecular mechanisms of action of commonly used bipolar disorder drugs. Methods: The transcriptional effects of bipolar disorder drug combination (lithium, valproate, lamotrigine and quetiapine) in cultured human neuronal cells were studied using next generation sequencing. Differential expression of genes ( n=20) and microRNAs ( n=6) was assessed and the differentially expressed microRNAs were confirmed with TaqMan MicroRNA Assays. The expression of the differentially expressed microRNAs were inhibited to determine bipolar disorder drug effects on their target genes ( n=8). Independent samples t-test was used for normally distributed data and Kruskal-Wallis/Mann-Whitney U test was used for data not distributed normally. Significance levels were set at p<0.05. Results: We found that bipolar disorder drugs tended to increase the expression of miR-128 and miR-378 ( p<0.05). Putative target genes of these microRNAs targeted pathways including those identified as “neuron projection development” and “axonogenesis”. Many of the target genes are inhibitors of neurite outgrowth and neurogenesis and were downregulated following bipolar disorder drug combination treatment (all p<0.05). The bipolar disorder drug combination tended to decrease the expression of the target genes ( NOVA1, GRIN3A, and VIM), however this effect could be reversed by the application of microRNA inhibitors. Conclusions: We conclude that at a transcriptional level, bipolar disorder drugs affect several genes in concert that would increase neurite outgrowth and neurogenesis and hence neural plasticity, and that this effect is mediated (at least in part) by modulation of the expression of these two key microRNAs.

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An introduction to microRNAs and their dysregulation in psychiatric disorders

Cited by 10 publications

References 77 publications

LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors

LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors

Analyzing the Role of MicroRNAs in Schizophrenia in the Context of Common Genetic Risk Variants

Drugs used to treat bipolar disorder act via microRNAs to regulate expression of genes involved in neurite outgrowth

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