scholarly journals Assessing the role of long-noncoding RNA in nucleus accumbens in subjects with alcohol dependence

2019 ◽  
Author(s):  
Gowon O. McMichael ◽  
John Drake ◽  
Eric Sean Vornholt ◽  
Kellen Cresswell ◽  
Vernell Williamson ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Alcohol Dependence ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Enrichment Analysis ◽  
Protein Coding ◽  
Network Analyses ◽  
Snp Data ◽  
The Brain

AbstractRecently, long noncoding RNA (lncRNA) were implicated in the etiology of alcohol dependence (AD). As lncRNA provide another layer of complexity to the transcriptome, assessing their expression in the brain is the first critical step towards understanding lncRNA functions in AD. To that end, we profiled the expression of lncRNA and protein coding genes (PCG) in nucleus accumbens (NAc) from 41 subjects with AD and 41 controls. At false discovery rate (FDR) of 5%, we identified 69 and 309 differentially expressed lncRNA and PCG genes, respectively. Using co-expression network analyses, we identified three lncRNA and five PCG modules significantly correlated with AD at Bonferroni adj. p≤0.05. To better understand lncRNA functions, we integrated the lncRNA and PCG hubs from the significant AD modules; at FDR of 5%, we identified 3 151 positive and 2 255 negative correlations supporting the functional role of lncRNA in the development of AD. Gene enrichment analysis revealed that PCG significantly correlated with lncRNA are, among others, enriched for neuronal and immune related processes. To highlight the mechanisms, by which genetic variants contribute to AD, we integrated lncRNA and PCG hubs with genome-wide SNP data. At FDR≤0.3, we identified 276 expression quantitative trait loci (eQTL), affecting the expression of 20 and 256 lncRNA and PCG hubs, respectively. Our study is the first to profile lncRNA expression in nucleus accumbens in a large postmortem alcohol brain sample and our results may provide novel insights into the regulation of the brain transcriptome across disease.

scholarly journals Assessing the Role of Long Noncoding RNA in Nucleus Accumbens in Subjects With Alcohol Dependence

2020 ◽  
Vol 44 (12) ◽  
pp. 2468-2480
Author(s):  
John Drake ◽  
Gowon O. McMichael ◽  
Eric Sean Vornholt ◽  
Kellen Cresswell ◽  
Vernell Williamson ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Alcohol Dependence ◽  
Long Noncoding Rna ◽  
Noncoding Rna

scholarly journals On the discovery of ADRAM, an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3

2021 ◽  
Author(s):  
XIang Li ◽  
Qiongyi Zhao ◽  
Ziqi Wang ◽  
Wei-Siang Liau ◽  
Dean Basic ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Large Population ◽  
Regulation Of Gene Expression ◽  
Fear Extinction ◽  
Early Gene ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Chaperone Protein ◽  
The Brain

Long-noncoding RNA (lncRNA) comprise a new class of genes that have been assigned key roles in development and disease. Many lncRNAs are specifically transcribed in the brain where they regulate the expression of protein-coding genes that underpin neuronal function; however, their role in learning and memory remains largely unexplored. We used RNA Capture-Seq to identify a large population of lncRNAs that are expressed in the infralimbic cortex of adult male mice in response to fear-related learning, with 14.5% of these annotated in the GENCODE database as lncRNAs with no known function. We combined these data with cell-type-specific ATAC-seq on neurons that had been selectively activated by fear-extinction learning, and revealed 434 lncRNAs derived from enhancer regions in the vicinity of protein-coding genes. In particular, we discovered an experience-induced lncRNA called ADRAM that acts as both a scaffold and a combinatorial guide to recruit the brain-enriched chaperone protein 14-3-3 to the promoter of the memory-associated immediate early gene Nr4a2. This leads to the expulsion of histone deactylases 3 and 4, and the recruitment of the histone acetyltransferase creb binding protein, which drives learning-induced Nr4a2 expression. Knockdown of ADRAM disrupts this interaction, blocks the expression of Nr4a2, and ultimately impairs the formation of fear-extinction memory. This study expands the lexicon of experience-dependent lncRNA activity in the brain, highlights enhancer-derived RNAs (eRNAs) as key players in the epigenetic regulation of gene expression associated with fear extinction, and suggests eRNAs, such as ADRAM, may constitute viable targets in developing novel treatments for fear-related anxiety disorders.

scholarly journals A cAMP/PKA-dependent synaptically targeted lncRNA mediates structural plasticity in hippocampal neurons by functionally interacting with the Spectrin/Ankyrin Network

2020 ◽  
Author(s):  
Eddie Grinman ◽  
Yoshihisa Nakahata ◽  
Yosef Avchalumov ◽  
Isabel Espadas ◽  
Supriya Swarnkar ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Long Noncoding Rna ◽  
Hippocampal Neurons ◽  
Noncoding Rna ◽  
Molecular Motor ◽  
Structural Plasticity ◽  
Dependent Manner ◽  
Protein Coding ◽  
Activity Dependent

AbstractActivity-dependent structural plasticity at the synapse requires specific changes in the neuronal transcriptome. While much is known about the role of coding elements in this process, the role of the long-noncoding transcriptome remains elusive. Here we report the discovery of an intronic long noncoding RNA (lncRNA)—termed ADEPTR—whose expression is upregulated and is synaptically transported in a cAMP/PKA-dependent manner in hippocampal neurons, independent of its protein-coding host gene. Loss of ADEPTR function suppresses activity-dependent changes in synaptic transmission and structural plasticity of dendritic spines. Mechanistically, dendritic localization of ADEPTR is mediated by molecular motor protein Kif2A. ADEPTR physically binds to actin-scaffolding regulators Ankyrin (AnkB) and Spectrin (Sptn1) and is required for their dendritic localization. Taken together, this study demonstrates that ADEPTR regulates the dendritic Spectrin-Ankyrin network for structural plasticity at the synapse and illuminates a novel role for lncRNAs at the synapse.One Sentence SummaryWe have uncovered an intronic long noncoding RNA that is synaptically transported in a cAMP-dependent manner and is linked to cytoskeletal components of structural plasticity in hippocampal neurons.

scholarly journals The Role of Neuropeptide Y in the Nucleus Accumbens

2021 ◽  
Vol 22 (14) ◽  
pp. 7287
Author(s):  
Masaki Tanaka ◽  
Shunji Yamada ◽  
Yoshihisa Watanabe
Keyword(s):  
Nervous System ◽  
Nucleus Accumbens ◽  
Neuropeptide Y ◽  
Emotional Behavior ◽  
Characteristic Functions ◽  
Receptor Subtypes ◽  
Neuroendocrine Mechanisms ◽  
Fear And Anxiety ◽  
The Brain

Neuropeptide Y (NPY), an abundant peptide in the central nervous system, is expressed in neurons of various regions throughout the brain. The physiological and behavioral effects of NPY are mainly mediated through Y1, Y2, and Y5 receptor subtypes, which are expressed in regions regulating food intake, fear and anxiety, learning and memory, depression, and posttraumatic stress. In particular, the nucleus accumbens (NAc) has one of the highest NPY concentrations in the brain. In this review, we summarize the role of NPY in the NAc. NPY is expressed principally in medium-sized aspiny neurons, and numerous NPY immunoreactive fibers are observed in the NAc. Alterations in NPY expression under certain conditions through intra-NAc injections of NPY or receptor agonists/antagonists revealed NPY to be involved in the characteristic functions of the NAc, such as alcohol intake and drug addiction. In addition, control of mesolimbic dopaminergic release via NPY receptors may take part in these functions. NPY in the NAc also participates in fat intake and emotional behavior. Accumbal NPY neurons and fibers may exert physiological and pathophysiological actions partly through neuroendocrine mechanisms and the autonomic nervous system.

scholarly journals Involvement of the long noncoding RNA H19 in osteogenic differentiation and bone regeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zimo Zhou ◽  
Mohammad Showkat Hossain ◽  
Da Liu
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Osteoblast Differentiation ◽  
Osteoclast Differentiation ◽  
Complex Processes ◽  
Osteogenic Induction ◽  
Novel Target

AbstractOsteogenic differentiation and bone regeneration are complex processes involving multiple genes and multiple steps. In this review, we summarize the effects of the long noncoding RNA (lncRNA) H19 on osteogenic differentiation.Osteogenic differentiation includes matrix secretion and calcium mineralization as hallmarks of osteoblast differentiation and the absorption of calcium and phosphorus as hallmarks of osteoclast differentiation. Mesenchymal stem cells (MSCs) form osteoprogenitor cells, pre-osteoblasts, mature osteoblasts, and osteocytes through induction and differentiation. lncRNAs regulate the expression of coding genes and play essential roles in osteogenic differentiation and bone regeneration. The lncRNA H19 is known to have vital roles in osteogenic induction.This review highlights the role of H19 as a novel target for osteogenic differentiation and the promotion of bone regeneration.

scholarly journals Role of Long Noncoding RNA 799 in the Metastasis of Cervical Cancer through Upregulation of TBL1XR1 Expression

2018 ◽  
Vol 13 ◽  
pp. 580-589 ◽  
Author(s):  
Ling-Min Liao ◽  
Feng-Hao Zhang ◽  
Gong-Ji Yao ◽  
Su-Feng Ai ◽  
Min Zheng ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna

scholarly journals LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Valentina Profumo ◽  
Barbara Forte ◽  
Stefano Percio ◽  
Federica Rotundo ◽  
Valentina Doldi ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Basal Cell ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Host Gene ◽  
Leader Role

scholarly journals An epithelial–mesenchymal transition-related long noncoding RNA signature correlates with the prognosis and progression in patients with bladder cancer

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Hang Tong ◽  
Tinghao Li ◽  
Shun Gao ◽  
Hubin Yin ◽  
Honghao Cao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Risk Groups ◽  
Functional Enrichment ◽  
Diagnostic Efficacy ◽  
Mesenchymal Transition

Abstract Bladder cancer is a common malignant tumour worldwide. Epithelial–mesenchymal transition (EMT)-related biomarkers can be used for early diagnosis and prognosis of cancer patients. To explore, accurate prediction models are essential to the diagnosis and treatment for bladder cancer. In the present study, an EMT-related long noncoding RNA (lncRNA) model was developed to predict the prognosis of patients with bladder cancer. Firstly, the EMT-related lncRNAs were identified by Pearson correlation analysis, and a prognostic EMT-related lncRNA signature was constructed through univariate and multivariate Cox regression analyses. Then, the diagnostic efficacy and the clinically predictive capacity of the signature were assessed. Finally, Gene set enrichment analysis (GSEA) and functional enrichment analysis were carried out with bioinformatics. An EMT-related lncRNA signature consisting of TTC28-AS1, LINC02446, AL662844.4, AC105942.1, AL049840.3, SNHG26, USP30-AS1, PSMB8-AS1, AL031775.1, AC073534.1, U62317.2, C5orf56, AJ271736.1, and AL139385.1 was constructed. The diagnostic efficacy of the signature was evaluated by the time-dependent receiver-operating characteristic (ROC) curves, in which all the values of the area under the ROC (AUC) were more than 0.73. A nomogram established by integrating clinical variables and the risk score confirmed that the signature had a good clinically predict capacity. GSEA analysis revealed that some cancer-related and EMT-related pathways were enriched in high-risk groups, while immune-related pathways were enriched in low-risk groups. Functional enrichment analysis showed that EMT was associated with abundant GO terms or signaling pathways. In short, our research showed that the 14 EMT-related lncRNA signature may predict the prognosis and progression of patients with bladder cancer.

scholarly journals An angiogenesis-related long noncoding RNA signature correlates with prognosis in patients with hepatocellular carcinoma

2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Dengliang Lei ◽  
Yue Chen ◽  
Yang Zhou ◽  
Gangli Hu ◽  
Fang Luo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Enrichment Analysis ◽  
Clinical Information ◽  
Roc Curves ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Highly Correlated

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide. Neovascularization is closely related to the malignancy of tumors. We constructed a signature of angiogenesis-related long noncoding RNA (lncRNA) to predict the prognosis of patients with HCC. The lncRNA expression matrix of 424 HCC patients was downloaded from The Cancer Genome Atlas (TCGA). First, gene set enrichment analysis (GSEA) was used to distinguish the differentially expressed genes of the angiogenesis genes in liver cancer and adjacent tissues. Next, a signature of angiogenesis-related lncRNAs was constructed using univariate and multivariate analyses, and receiver operating characteristic (ROC) curves were used to assess the accuracy. The signature and relevant clinical information were used to construct the nomogram. A 5-lncRNA signature was highly correlated with overall survival (OS) in HCC patients and performed well in evaluations using the C-index, areas under the curve, and calibration curves. In summary, the 5-lncRNA model can serve as an accurate signature to predict the prognosis of patients with liver cancer, but its mechanism of action must be further elucidated by experiments.

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