Sex-specific up-regulation of lncRNAs in peripheral blood of patients with schizophrenia

Fallah, Hossein; Azari, Iman; Neishabouri, Seyedeh Morvarid; Oskooei, Vahid Kholghi; Taheri, Mohammad; Ghafouri‐Fard, Soudeh

doi:10.1038/s41598-019-49265-z

Cited by 44 publications

(30 citation statements)

References 45 publications

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“…Table S1 summarizes the primers features. We have chosen B2M gene as the reference gene based on our previous observations regrading constant expression of this gene in peripheral blood of patients with schizophrenia 26 .…”

Section: Methodsmentioning

confidence: 99%

Expression of NF-κB associated lncRNAs in schizophrenia

Safa

Badrlou

Arsang‐Jang

et al. 2020

Sci Rep

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NF-κB signaling pathway has important roles in the regulation of growth and development of nervous system. This pathway has also been shown to participate in the pathogenesis of schizophrenia. Meanwhile, activity of NF-κB signaling pathway is regulated by several factors including non-coding RNAs (lncRNAs). In the current study, we evaluated expression of nine NF-κB-related lncRNAs namely DILC, ANRIL, PACER, CHAST, ADINR, DICER1-AS1, HNF1A-AS1, H19 and NKILA as well as two mRNA coding genes namely ATG5 and CEBPA in the peripheral blood of patients with schizophrenia compared with matched healthy subjects. Expressions of these genes were assessed by real time PCR technique. Expression of PACER was lower in patients with schizophrenia compared with controls (Posterior beta = − 0.684, P value = 0.049). On the other hand, expressions of CHAST, CEBPA, H19, HNF1A-AS1 and DICER1-AS1 were higher in patients compared with controls (Posterior beta = 0.39, P value = 0.005; Posterior beta = 0.844, P value < 0.0001; Posterior beta = 0.467, P value < 0.0001; Posterior beta = 1.107, P value = 0.005; Posterior beta = 0.176, P value = 0.044, respectively). We also appraised the diagnostic power of transcript quantities of CHAST, CEBPA, DICER1-AS1, H19 and HNF1A-AS1 in distinguishing between patients with schizophrenia and controls through depicting ROC curves. Based on the area under curve (AUC) values, CEBPA had the best diagnostic power (AUC = 0.948, P < 0.0001), followed by H19 (AUC = 0.815, P < 0.0001). Taken together, our study demonstrated dysregulation of NF-κB-related lncRNAs and genes in the peripheral blood of patients with schizophrenia and their potential as peripheral markers for this psychiatric condition.

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Section: Methodsmentioning

confidence: 99%

Expression of NF-κB associated lncRNAs in schizophrenia

Safa

Badrlou

Arsang‐Jang

et al. 2020

Sci Rep

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“…A recent study has reported higher expression of both HOXA-AS2 and SPRY4-IT1 in patients with schizophrenia compared with controls. Contradictory to the present study, when authors assessed expression of these genes in gender-based manner, the differences in the expression of these lncRNAs were remarkable only among females (Fallah et al, 2019). These findings suggest different roles of these lncRNAs based on the gender of patients.…”

Section: Discussionmentioning

confidence: 74%

Epilepsy Is Associated With Dysregulation of Long Non-coding RNAs in the Peripheral Blood

Hashemian

Ghafouri‐Fard

Arsang‐Jang

et al. 2019

Front. Mol. Biosci.

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Background: Long non-coding RNAs (lncRNAs) are a group of functional transcripts that are not translated to proteins. Recent investigations have underscored their role in the pathogenesis of neurodevelopmental disorders.Methods: In the current investigation, we quantified expression levels of four lncRNAs (HOXA-AS2, SPRY4-IT1, MEG3, and LINC-ROR) in peripheral blood of epileptic patients and normal controls.Results: Expression of HOXA-AS2 was significantly higher in patients compared with controls (Posterior beta = 1.982, P = 0.001). We detected interaction effects of gender on expression of HOXA-AS2 (P = 0.012). Further analyses showed over-expression of HOXA-AS2 in male patients compared with male controls (P = 0.003), in spite of similar levels of expression between female cases and female controls (P = 0.77). Expression of SPRY4-IT1 was higher in total patients compared with total controls (Posterior beta = 1.27, P = 0.02). Such difference was only observed between male patients and male controls when dividing study participants based on their gender (P = 0.012). There was no significant difference in expression of MEG3 and LINC-ROR between patients and controls.Conclusion: Expression levels of all lncRNAs were correlated with each other with r values ranging from 0.61 to 0.76 (P < 0.0001). However, expressions of none of lncRNAs were correlated with age of study participants. The current data implies a putative role for two lncRNAs in the pathogenesis of epilepsy and warrants future functional studies to verify the observed association.

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“…In the first example, we identify MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) as an NDD-related enhancer-ncRNA, located within chromosome 11 with 12.7kb in length; this lncRNA is highly expressed in neurons [32]. It has been shown that the loss of the MALAT1 negatively affects the expression of neighboring genes, including genes which are significantly decreased in expression within several brain regions relevant to schizophrenia [33]. Furthermore, a study reported that MALAT1 expression was significantly different in patients with schizophrenia compared with healthy subjects [34], and MALAT1 is also implicated in ASD [35].…”

Section: Resultsmentioning

confidence: 99%

“…It has been shown that the loss of the MALAT1 negatively affects the expression of neighboring genes, including genes which are significantly decreased in expression within several brain regions relevant to schizophrenia [33]. Furthermore, a study reported that MALAT1 expression was significantly different in patients with schizophrenia compared with healthy subjects [34], and MALAT1 is also implicated in ASD [35].…”

Section: Association Of Enhancer Ncrnas With Decipher Phenotypesmentioning

confidence: 99%

Evidence for enhancer noncoding RNAs (enhancer-ncRNAs) with gene regulatory functions relevant to neurodevelopmental disorders

Asgari

Heng

Lovell

et al. 2020

Preprint

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Noncoding RNAs (ncRNAs) comprise a significant proportion of the mammalian genome, but their biological significance in neurodevelopment and in diseases is poorly understood. In this study, we have performed a genome-wide investigation of human noncoding RNAs for cell regulatory functions in brain tissue. By analysing ENCODE regulatory features, associations with FANTOM5 tissue-specific enhancers, as well as tissue-specific expression profiles, we have identified 17,743 noncoding RNAs comprising at least one nervous system-related expression Quantitative TraitLoci (eQTL) polymorphism that is associated with protein coding genes. Of these, 908 brain-enriched noncoding RNAs (comprising 907 long noncoding RNAs and 1 pseudogene) also overlap with chromatin states characterised as enhancers. Based 2 on these criteria, we referred to such noncoding RNAs with putative enhancer activity as brain 'enhancer-ncRNAs'. To investigate their impact in neurodevelopmental disorders, we integrated GWAS SNPs and Copy Number Variation (CNV) data and found that 265 enhancer-ncRNAs were either mutated (CNV deletion or duplication) or contain at least one GWAS SNPs in the context of such conditions. Of these, the eQTLassociated gene for 82 enhancer-ncRNAs did not overlap with either GWAS SNPs or CNVs. However, in 23 of these 82 enhancer-ncRNAs, eQTL interaction was explained solely by the presence of each of these noncoding RNAs, suggesting in such contexts that mutations to neurodevelopment gene enhancers disrupt ncRNA interaction. We also cross-referenced our data with the DECIPHER database of clinical phenotypes to find that mutations to 34 of the 82 enhancer-ncRNAs are significantly associated with phenotypes including behavioural abnormality, and cognitive impairment. Taken together, we provide evidence for a distinct set of brain-enriched ncRNAs that influence genomic enhancers during neurodevelopment, suggesting enhancer mutations may be relevant to the functions for such ncRNAs in neurodevelopmental disorders.

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Sex-specific up-regulation of lncRNAs in peripheral blood of patients with schizophrenia

Cited by 44 publications

References 45 publications

Expression of NF-κB associated lncRNAs in schizophrenia

Expression of NF-κB associated lncRNAs in schizophrenia

Epilepsy Is Associated With Dysregulation of Long Non-coding RNAs in the Peripheral Blood

Evidence for enhancer noncoding RNAs (enhancer-ncRNAs) with gene regulatory functions relevant to neurodevelopmental disorders

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