scholarly journals Coding and Non-Coding RNA Abnormalities in Bipolar Disorder

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 946 ◽  
Author(s):  
Luykx ◽  
Giuliani ◽  
Giuliani ◽  
Veldink
Keyword(s):  
Bipolar Disorder ◽  
Alternative Splicing ◽  
Brain Tissue ◽  
Molecular Mechanisms ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Large Reservoir ◽  
Non Coding Rna ◽  
Postmortem Brain Tissue ◽  
Alternative Splicing Events

The molecular mechanisms underlying bipolar disorder (BPD) have remained largely unknown. Postmortem brain tissue studies comparing BPD patients with healthy controls have produced a heterogeneous array of potentially implicated protein-coding RNAs. We hypothesized that dysregulation of not only coding, but multiple classes of RNA (coding RNA, long non-coding (lnc) RNA, circular (circ) RNA, and/or alternative splicing) underlie the pathogenesis of BPD. Using non-polyadenylated libraries we performed RNA sequencing in postmortem human medial frontal gyrus tissue from BPD patients and healthy controls. Twenty genes, some of which not previously implicated in BPD, were differentially expressed (DE). PCR validation and replication confirmed the implication of these DE genes. Functional in silico analyses identified enrichment of angiogenesis, vascular system development and histone H3-K4 demethylation. In addition, ten lncRNA transcripts were differentially expressed. Furthermore, an overall increased number of alternative splicing events in BPD was detected, as well as an increase in the number of genes carrying alternative splicing events. Finally, a large reservoir of circRNAs populating brain tissue not affected by BPD is described, while in BPD altered levels of two circular transcripts, cNEBL and cEPHA3, are reported. cEPHA3, hitherto unlinked to BPD, is implicated in developmental processes in the central nervous system. Although we did not perform replication analyses of non-coding RNA findings, our findings hint that RNA dysregulation in BPD is not limited to coding regions, opening avenues for future pharmacological investigations and biomarker research.

scholarly journals Coding and non-coding RNA dysregulation in bipolar disorder

2018 ◽  
Author(s):  
Jurjen J. Luykx ◽  
F. Giuliani ◽  
G. Giuliani ◽  
J.H. Veldink
Keyword(s):  
Bipolar Disorder ◽  
Alternative Splicing ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
Differentially Expressed ◽  
Postmortem Brain ◽  
Healthy Controls ◽  
Non Coding Rna ◽  
Postmortem Brain Tissue ◽  
Alternative Splicing Events

AbstractThe molecular mechanisms underlying bipolar disorder (BPD) have remained largely unknown. Postmortem brain tissue studies comparing BPD patients with healthy controls have produced a heterogeneous array of potentially implicated protein-coding RNAs. We hypothesized that dysregulation of not only coding, but multiple classes of RNA (coding RNA, long non-coding (lnc) RNA, circular (circ) RNA, and/or alternative splicing) underlie the pathogenesis of BPD. Using non-polyadenylated libraries we performed RNA sequencing in postmortem human medial frontal gyrus tissue from BPD patients and healthy controls. We found twenty genes, some of which not previously implicated in BPD, differentially expressed. PCR validation and replication confirmed the implication of these DE genes. Functional analyses identified enrichment of angiogenesis, vascular system development and histone H3-K4 demethylation. In addition, ten lncRNA transcripts were differentially expressed. Furthermore, we detected an overall increased number of alternative splicing events in BPD, as well as an increase in the number of genes carrying alternative splicing events. Finally, we report altered levels of two circular transcripts, cNEBL and cEPHA3. In conclusion, our non-coding RNA findings demonstrate that RNA dysregulation in BPD is not limited to coding regions, opening avenues for future pharmacological investigations and biomarker research.

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

2020 ◽  
Vol 34 (3) ◽  
pp. 370-379 ◽  
Author(s):  
Srisaiyini Kidnapillai ◽  
Ben Wade ◽  
Chiara C Bortolasci ◽  
Bruna Panizzutti ◽  
Briana Spolding ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Neurite Outgrowth ◽  
Neural Plasticity ◽  
Drug Combination ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Drug Effects ◽  
Differentially Expressed ◽  
Transcriptional Level ◽  
Expression Of Genes

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.

scholarly journals Alternative splicing of leptin receptor overlapping transcript in osteosarcoma

2020 ◽  
Vol 245 (16) ◽  
pp. 1437-1443
Author(s):  
Emel Rothzerg ◽  
Xuan D Ho ◽  
Jiake Xu ◽  
David Wood ◽  
Aare Märtson ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Molecular Mechanisms ◽  
Leptin Receptor ◽  
Osteogenic Sarcoma ◽  
Differentially Expressed ◽  
Primary Malignancy ◽  
Transcript Variants ◽  
Potential Biomarker ◽  
Whole Transcriptome Analysis ◽  
Tumor Biopsies

Alternative splicing of RNA is an essential mechanism that increases proteomic diversity in eukaryotic cells. Aberrant alternative splicing is often associated with various human diseases, including cancer. We conducted whole-transcriptome analysis of 18 osteosarcoma bone samples (paired normal—tumor biopsies). Using RNA-seq, we identified statistically significant (FDR <0.05) 26 differentially expressed transcript variants of leptin receptor overlapping transcript ( LEPROT) gene. Some of the transcripts were overexpressed in normal cells, whereas others were overexpressed in tumor cells. The function of LEPROT is not completely understood. Herein, we highlight a possible association between OS and aberrant alternative splicing events and its interaction with the expression of LEPROT. We also discuss the role of LEPROT in regulating growth hormone and its receptor, and the relationship with initiation and progression of OS. This research study may help to understand the association of alternative splicing mechanism in OS and in tumorigenesis more generally. Further, LEPROT gene can also be considered as a potential biomarker of osteosarcoma. Impact statement Osteosarcoma (OS, also known as osteogenic sarcoma) is the most common primary malignancy of bone in children and adolescents. The molecular mechanisms of OS are extremely complicated and its molecular mediators remain to be elucidated. We sequenced total RNA from 18 OS bone samples (paired normal—tumor biopsies). We found statistically significant (FDR <0.05) 26 differentially expressed transcript variants of LEPROT gene with different expressions in normal and tumor samples. These findings contribute to the understanding of molecular mechanisms of OS development and provide encouragement to pursue further research.

scholarly journals mRNA and long non-coding RNA expression profiles in rats reveal inflammatory features in sepsis-associated encephalopathy

2017 ◽  
Author(s):  
WenChong Sun ◽  
Ling Pei ◽  
Zuodi Liang
Keyword(s):  
Brain Tissue ◽  
Transcriptome Sequencing ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Sprague Dawley ◽  
Non Coding Rna ◽  
Cognitive Sequelae ◽  
First Time ◽  
Long Non Coding Rna

AbstractBackgroundSepsis-associated encephalopathy (SAE) is related to cognitive sequelae in patients in the intensive care unit (ICU) and can have serious impacts on quality of life after recovery. Although various pathogenic pathways are involved in SAE development, little is known concerning the global role of long non-coding RNAs (lncRNAs) in SAE.MethodsHerein, we employed transcriptome sequencing approaches to characterize the effects of lipopolysaccharide (LPS) on lncRNA expression patterns in brain tissue isolated from Sprague-Dawley (SD) rats with and without SAE. We performed high-throughput transcriptome sequencing after LPS was intraperitoneally injected and predicted targets and functions using bioinformatics tools. Subsequently, we explored the results in detail according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.ResultsLncRNAs were differentially expressed in brain tissue after LPS treatment. After 6 h of LPS exposure, expression of 400 lncRNAs were significantly changed, including an increase in 316 lncRNAs and a decrease in 84 lncRNAs. In addition, 155 mRNAs were differentially expressed, with 84 up-regulated and 71 down-regulated. At 24 h post-treatment, expression of 117 lncRNAs and 57 mRNAs was consistently elevated, while expression of 79 lncRNAs and 21 mRNAs was decreased (change > 1.5-fold; p < 0.05). We demonstrated for the first time that differentially expressed lncRNAs were predicted to be enriched in a post-chaperonin tubulin folding pathway (GO : 007023), which is closely related to the key step in the tubulin folding process.Interestingly, the predicted pathway (KEGG 04360: axon guidance) was significantly changed under the same conditions. These results reveal that LPS might influence the construction and polarization of microtubules, which exert predominant roles in synaptogenesis and related biofunctions in the rodent central nervous system (CNS).ConclusionsAn inventory of LPS-modulated expression profiles from the rodent CNS is an important step toward understanding the function of mRNAs, including lncRNAs, and suggests that microtubule malformation and dysfunction may be involved in SAE pathogenesis.

scholarly journals Identification of Non-coding RNA Biomarkers in Stress-induced Depression via Comprehensive Analysis of Competing Endogenous RNA Network

2020 ◽  
Author(s):  
xuanjun liu ◽  
Lan Yan ◽  
Chun Lin ◽  
Yiliang Zhang ◽  
Haofei Miao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Comprehensive Analysis ◽  
Differentially Expressed ◽  
Psychiatric Disease ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Competing Endogenous Rna ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Promising Perspective

Abstract BackgroundDepression is one of the most common psychiatric disease worldwide. Although the research about the pathogenesis of depression have achieved progress, the detailed effect of non-coding RNAs (ncRNAs) in depression are still not clearly elucidated. This study was aimed to identify non-coding RNA biomarkers in stress-induced depression via comprehensive analysis of competing endogenous RNA networkMethodsIn this present study, we acquired RNA expression from RNA seq expression profile in three mice with depressive-like behaviors using chronic restraint stress paradigm and three C57BL/6J wild-type mice as control mice. ResultsA total of 41 differentially expressed circular RNAs (circRNAs) and 181 differentially expressed messenger RNAs (mRNAs) were up-regulated, and 65 differentially expressed circRNAs and 289 differentially expressed mRNAs were down-regulated, which were selected by a threshold of fold change ≥2 and a p-value < 0.05. Gene Ontology was performed to analyze the biological functions, and we predicted potential signaling pathways based on Kyoto Encyclopedia of Genes and Genomes pathway database. In addition, we constructed a circRNA-microRNA (miRNA)-mRNA regulatory network to further identify non-coding RNAs biomarkers. ConclusionsOur findings provide a promising perspective for further research into molecular mechanisms of depression, and targeting circRNA -mediated competing endogenous RNA (ceRNA) network is a useful strategy to early recognize the depression.

scholarly journals PO-046 Gene expression profiling of peripheral blood mononuclear cells in young male trampoline athletes

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Li Gao ◽  
Yong Jie Yang ◽  
En Qi Li ◽  
Jia Ning Mao
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Bone Health ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Healthy Controls ◽  
Mineral Density

Objective Evidence indicates that physical activity influence bone health. However, the molecular mechanisms mediating the beneficial adaptations to exercise are not well understood. The purpose of this study was to examine the differentially expressed genes in PBMC between athletes and healthy controls, and to analyze the important functional genes and signal pathways that cause increased bone mineral density in athletes, in order to further reveal the molecular mechanisms of exercise promoting bone health. Methods Five professional trampoline athletes and five age-matched untrained college students participated in this study. Used the human expression Microarray V4.0 expression profiling chip to detect differentially expressed genes in the two groups, and performed KEGG Pathway analysis and application of STRING database to construct protein interaction Network; Real-Time PCR technology was used to verify the expression of some differential genes.  Results Compared with healthy controls, there were significant improvement in lumbar spine bone mineral density, and 236 up-regulated as well as 265 down-regulated in serum samples of athletes. The differentially expressed genes involved 28 signal pathways, such as cell adhesion molecules. Protein interaction network showed that MYC was at the core node position. Real-time PCR results showed that the expression levels of CD40 and ITGα6 genes in the athletes were up-regulated compared with the healthy controls, the detection results were consistent with that of the gene chip. Conclusions The findings highlight that long-term high-intensity trampoline training could induce transcriptional changes in PBMC of the athletes. These data suggest that gene expression fingerprints can serve as a powerful research tool to design novel strategies for monitoring exercise. The findings of the study also provide support for the notion that PBMC could be used as a substitute to study exercise training that affects bone health.

Exploring the Potential Pathogenic Mechanisms of Asthma Deterioration Based on Modular Drivers

2021 ◽  
Vol 7 (4) ◽  
pp. 756-764
Author(s):  
Jianhua Liu ◽  
Liqing Zheng ◽  
Liang Cao ◽  
Changhong Zhang ◽  
Chen Li
Keyword(s):  
Cellular Response ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Hypergeometric Test ◽  
Asthmatic Patients ◽  
Pathogenic Genes ◽  
Non Coding Rna ◽  
Asthma Patients ◽  
Differential Genes

Asthma is a complicated chronic airway inflammatory disease caused by the interaction of genetic susceptibility and environmental impact. Although biologists have explored the pathogenesis of asthma in various aspects, the exact molecular mechanism continues to be elusive. In this study, we conducted a modular study of asthma-related genes to explore their core pathogenic driving genes. Firstly, the expression profiles of normal, mild to moderate and severe asthma patients were analyzed to screen the differentially expressed genes. Secondly, differential genes of asthma were integrated, co-expressed and clustered into modules. Next, enrichment of GO function and KEGG pathway of module genes were analyzed. Finally, non-coding RNA (ncRNA) and transcription factors that regulate modules are predicted by hypergeometric test. In summary, we have obtained 14 co-expression modules, among which CDCA5, JUNB and other genes are significantly differentially expressed in asthmatic patients, and have an active regulatory role in dysfunction module, so they are recognized as asthma-driving genes. Enrichment results showed that module genes were significantly involved in cell growth, transcription factor activity, cellular response to drugs and the transport of various ions. In addition, they also radically regulate Wnt, TGF-beta, JAK-STAT and extracellular matrix signaling pathways. Finally, we identified significant regulatory dysfunction modules of ncRNA pivot (including miR-181a-5p and let-7d-5p) and TF pivot (including NFKB1, ESR1 and MYC). Overall, our work has uncovered a co-expression network involved in the regulation of core pathogenic genes of asthma. It helps to reveal the core dysfunction modules and potential regulatory factors of this disease, and to enhance our understanding of the molecular mechanisms of asthma-related diseases.

Sign in / Sign up

Export Citation Format

Share Document