The importance of long non-coding RNAs in neuropsychiatric disorders

Hosseini, Ebrahim; Bagheri‐Hosseinabadi, Zahra; Toma, Ilario De; Jafarisani, Moslem; Sadeghi, Iman

doi:10.1016/j.mam.2019.07.004

Cited by 56 publications

(43 citation statements)

References 193 publications

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“…Long intergenic noncoding RNAs (lincRNAs) are lncRNA which do not overlap protein-coding genes. LncRNAs are important regulators in human disease and have been associated with drug addiction [46]. LncRNAs are involved in gene expression, chromatin remodeling, RNA stabilization and transcription regulation with tissue specificity but their contribution to the development of drug addiction is largely unknown [47, 48].…”

Section: Discussionmentioning

confidence: 99%

A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction

et al. 2019

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There is a reciprocal relationship between the circadian and the reward systems. Polymorphisms in several circadian rhythm-related (clock) genes were associated with drug addiction. This study aims to search for associations between 895 variants in 39 circadian rhythm-related genes and opioid addiction (OUD). Genotyping was performed with the Smokescreen® array. Ancestry was verified by principal/MDS component analysis and the sample was limited to European Americans (EA) (OUD; n = 435, controls; n = 138). Nominally significant associations (p < 0.01) were detected for several variants in genes encoding vasoactive intestinal peptide receptor 2 (VIPR2), period circadian regulator 2 (PER2), casein kinase 1 epsilon (CSNK1E), and activator of transcription and developmental regulator (AUTS2), but no signal survived correction for multiple testing. There was intriguing association signal for the untranslated region (3’ UTR) variant rs885863 in VIPR2, (p = .0065; OR = 0.51; 95% CI 0.31–0.51). The result was corroborated in an independent EA OUD sample (n = 398, p = 0.0036; for the combined samples). Notably, this SNP is an expression quantitative trait locus (cis-eQTL) for VIPR2 and a long intergenic non-coding RNA, lincRNA 689, in a tissue-specific manner, based on the Genotype-Tissue Expression (GTEx) project. Vasoactive intestinal peptide (VIP) is an important peptide of light-activated suprachiasmatic nucleus cells. It regulates diverse physiological processes including circadian rhythms, learning and memory, and stress response. This is the first report of an association of a VIPR2 variant and OUD. Additionally, analysis of combinations of single nucleotide polymorphisms (SNPs) genotypes revealed an association of PER2 SNP rs80136044, and SNP rs4128839, located 41.6 kb downstream of neuropeptide Y receptor type 1 gene, NPY1R (p = 3.4 × 10−6, OR = 11.4, 95% CI 2.7–48.2). The study provides preliminary insight into the relationship between genetic variants in circadian rhythm genes and long non-coding RNA (lncRNAs) in their vicinity, and opioid addiction.

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Section: Discussionmentioning

confidence: 99%

A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction

et al. 2019

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“…Long ncRNAs play crucial roles in human beings, not only do lncRNAs participate in regulating normal mammalian gene expression function or other body biological processes, but also they have notable influences on human diseases, such as various cancers, neuropsychiatric disorders and atherosclerosis 88‐90 . Apparently, there are gradually increasing explorations in the mechanism of lncRNAs functioning in TNBC in recent years.…”

Section: Long Non‐coding Rnasmentioning

confidence: 99%

Systematic characterization of non‐coding RNAs in triple‐negative breast cancer

et al. 2020

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Triple‐negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer with negativity for oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2). Non‐coding RNAs (ncRNAs) make up most of the transcriptome and are widely present in eukaryotic cells. In recent years, emerging evidence suggests that ncRNAs, mainly microRNAs (miRNAs), long ncRNAs (lncRNAs) and circular RNAs (circRNAs), play prominent roles in the tumorigenesis and development of TNBC, but the functions of most ncRNAs have not been fully described. In this review, we systematically elucidate the general characteristics and biogenesis of miRNAs, lncRNAs and circRNAs, discuss the emerging functions of these ncRNAs in TNBC and present future perspectives in clinical practice.

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“…Site-specific DNA methylation by DNMT1 was proposed to be mediated by long non-coding RNAs (lncRNAs), preventing or promoting DNMT1 binding ( Chalei et al, 2014 ). Indeed, there is accumulating evidence for the significance of lncRNAs impairment in several neuropsychiatric diseases including ASD, schizophrenia, intellectual disability, major depressive disorder and others ( Hosseini et al, 2019 ).…”

Section: Dna Methylation and Dnmts In Interneuron Functionality In Hementioning

confidence: 99%

DNA Methylation-Dependent Dysregulation of GABAergic Interneuron Functionality in Neuropsychiatric Diseases

Linde

Zimmer-Bensch

2020

Front. Neurosci.

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Neuropsychiatric diseases, such as mood disorders, schizophrenia, and autism, represent multifactorial disorders, differing in causes, disease onset, severity, and symptoms. A common feature of numerous neuropsychiatric conditions are defects in the cortical inhibitory GABAergic system. The balance of excitation and inhibition is fundamental for proper and efficient information processing in the cerebral cortex. Thus, altered inhibition is suggested to account for pathological symptoms like cognitive impairments and dysfunctional multisensory integration. While it became apparent that most of these diseases have a clear genetic component, environmental influences emerged as an impact of disease manifestation, onset, and severity. Epigenetic mechanisms of transcriptional control, such as DNA methylation, are known to be responsive to external stimuli, and are suspected to be implicated in the functional impairments of GABAergic interneurons, and hence, the pathophysiology of neuropsychiatric diseases. Here, we provide an overview about the multifaceted functional implications of DNA methylation and DNA methyltransferases in cortical interneuron development and function in health and disease. Apart from the regulation of gamma-aminobutyric acid-related genes and genes relevant for interneuron development, we discuss the role of DNA methylation-dependent regulation of synaptic transmission by the modulation of endocytosis-related genes as potential pathophysiological mechanisms underlying neuropsychiatric conditions. Deciphering the hierarchy and mechanisms of changes in epigenetic signatures is crucial to develop effective strategies for treatment and prevention.

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The importance of long non-coding RNAs in neuropsychiatric disorders

Cited by 56 publications

References 193 publications

A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction

A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction

Systematic characterization of non‐coding RNAs in triple‐negative breast cancer

DNA Methylation-Dependent Dysregulation of GABAergic Interneuron Functionality in Neuropsychiatric Diseases

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