scholarly journals The Long Noncoding RNA Differential Expression in Peripheral Blood Leukocyte from Schizophrenia Patients by RNA Sequencing

2020 ◽  
Author(s):  
Jie Wu ◽  
Zijun Liu ◽  
Yunqiao Zhang ◽  
Zhaowei Teng ◽  
Xu You ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Correlation Coefficient ◽  
Peripheral Blood ◽  
Noncoding Rna ◽  
Clinical Symptoms ◽  
Function Analysis ◽  
Hierarchical Classification ◽  
Peripheral Blood Leukocyte ◽  
Protein Coding ◽  
Functional Sites

Abstract Background: The diagnosis of schizophrenia (SCZ) depends on the evaluation of clinical symptoms, and there is no objective biomarker. Surveys have found that long non-coding RNA (lncRNA) may be affected in the pathogenesis of SCZ. There are also different genes in the expression of peripheral blood (PBL) in SCZ patients.Methods: We profiled transcriptome analysis of PBL in 50 patients with schizophrenia and 50 controls without psychiatric diagnoses, reconstructed PBL transcriptome information using RNA-seq, predicted lncRNA-mRNA interaction via “RNAplex”, a hierarchical classification-Spielman correlation coefficient approach was used to analyze the correlation between lncRNA and protein-coding gene expression among samples, and used systematic bioinformatics methods (Go/Pathway) to perform lncRNA functional annotation and qPCR experimental verification. Predicting functional sites for sequences using the database PROSITE, NCBI, UCSC, JASPAR.Results: We screened 94 lncRNA and 1179 mRNA differential expressions in PBL, of which 46 new lncRNAs were identified for the first time. Enrichment into lncRNA involves biological processes and signaling pathways related to the neutrophil activation involved in immune response. According to Spearman correlation coefficient analysis, 81 lncRNA and 410 mRNA have expression correlation (p<0.01 and |r|≥0.4), QPCR in independent samples verified that the core node of the lncRNA-mRNA co-expression network IL1RAP-TCONS_00138311 variable shear is indeed highly expressed in SCZ patients, 2^-△△Ct is 0.56, the area under the ROC curve is 0.924. The top four ranked transcription factors were predicted to be HSF1, HSF2, HSF4, and FOXA1.Conclusions: Combined with sequence function analysis, it showed that the transcription factors FOXA1, HSF1, HSF2, HSF4, etc. may mediate the activation of IL1B-induced NF-kβ pathway and other inflammatory pathways through the regulation of IL1RAP alternative splicing transcripts TCONS_00138311, thereby participating in the pathogenesis of SCZ. We propose that the frequency of Differential lncRNA in peripheral blood could be used as novel biomarker for distinguishing SCZ from health.

scholarly journals Differential Expression of Long Noncoding RNAs in Peripheral Blood Leukocytes of Patients with Schizophrenia

2021 ◽  
Author(s):  
Jie Wu ◽  
Zijun Liu ◽  
Yunqiao Zhang ◽  
Zhaowei Teng ◽  
Xu You ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Correlation Coefficient ◽  
Peripheral Blood ◽  
Clinical Symptoms ◽  
Function Analysis ◽  
Hierarchical Classification ◽  
Differentially Expressed ◽  
Blood Leukocytes ◽  
Functional Sites

Abstract Background: The diagnosis of schizophrenia (SCZ) depends on the evaluation of clinical symptoms, but there is no objective biomarker. Studies have shown that long non-coding RNAs (lncRNAs) may be involved in the pathogenesis of SCZ. In this study, we evaluated the differential gene expression of lncRNAs and mRNAs in peripheral blood (PBL) of patients with SCZ.Methods: We profiled the transcriptome of PBL in 50 patients with SCZ and 50 controls without psychiatric diagnoses, using RNA-seq. LncRNA-mRNA interactions were predicted using “RNAplex”, a hierarchical classification-Spielman correlation coefficient approach was used to analyze the correlation between lncRNAs and protein-coding gene expression among samples, and systematic bioinformatic methods (Go/Pathway) were used to perform lncRNA functional annotation. The results were validated using qPCR. Functional sites in sequences were predicted using the PROSITE, NCBI, UCSC, and JASPAR databases.Results: We identified 94 lncRNAs and 1179 mRNAs differentially expressed in PBL, of which 46 lncRNAs were identified for the first time. Enrichment of lncRNAs involved biological processes and signaling pathways related to neutrophil activation involved in the immune response. Spearman correlation coefficient analysis showed that 81 lncRNAs and 410 mRNAs had correlated expression (p < 0.01 and |r| ≥ 0.4). qPCR performed on independent samples verified that the core node of the lncRNA-mRNA co-expression network, the IL1RAP-TCONS_00138311 variable splicing transcript, was highly expressed in patients with SCZ (2△△Ct of 0.56, area under the ROC curve of 0.924). The top four ranked transcription factors were predicted to be HSF1, HSF2, HSF4, and FOXA1.Conclusions: Combined with sequence function analysis, we showed that the transcription factors FOXA1, HSF1, HSF2, and HSF4 may mediate the activation of IL1B-induced NF-kβ pathway and other inflammatory pathways through regulation of the IL1RAP alternative splicing transcript TCONS_00138311, thereby participating in the pathogenesis of SCZ. We propose that the frequency of differentially expressed lncRNAs in PBL may serve as a novel biomarker for diagnosis of SCZ.

scholarly journals Cannabidiol Regulates Gene Expression in Encephalitogenic T cells Using Histone Methylation and noncoding RNA during Experimental Autoimmune Encephalomyelitis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xiaoming Yang ◽  
Marpe Bam ◽  
Prakash S. Nagarkatti ◽  
Mitzi Nagarkatti
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Transcription Factors ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Histone Methylation ◽  
Noncoding Rna ◽  
Immune Modulation ◽  
Clinical Symptoms ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Abstract Cannabidiol (CBD) has been shown by our laboratory to attenuate experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). In this study, we used microarray and next generation sequencing (NGS)-based approaches to determine whether CBD would alter genome-wide histone modification and gene expression in MOG sensitized lymphocytes. We compared H3K4me3 and H3K27me3 marks in CD4+ T cells from naïve, EAE and CBD treated EAE mice by ChIP-seq. Although the overall methylation level of these two histone marks did not change significantly, the signal intensity and coverage differed in individual genes, suggesting that CBD may modulate gene expression by altering histone methylation. Further analysis showed that these histone methylation signals were differentially enriched in the binding sites of certain transcription factors, such as ZNF143 and FoxA1, suggesting that these transcription factors may play important roles in CBD mediated immune modulation. Using microarray analysis, we found that the expression pattern of many EAE-induced genes was reversed by CBD treatment which was consistent with its effect on attenuating the clinical symptoms of EAE. A unique finding of this study was that the expression of many miRNAs and lncRNAs was dramatically affected by CBD. In summary, this study demonstrates that CBD suppresses inflammation through multiple mechanisms, from histone methylation to miRNA to lncRNA.

scholarly journals Classifying gastric cancer using FLORA reveals clinically relevant molecular subtypes and highlights LINC01614 as a biomarker for patient prognosis

Oncogene ◽  
2021 ◽  
Author(s):  
Yiyun Chen ◽  
Wing Yin Cheng ◽  
Hongyu Shi ◽  
Shengshuo Huang ◽  
Huarong Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rna ◽  
Molecular Subtype ◽  
Sequencing Data ◽  
Cell Growth And Migration ◽  
Protein Coding ◽  
Over Expression ◽  
And Migration ◽  
Patient Prognosis ◽  
Subtype 3

AbstractMolecular-based classifications of gastric cancer (GC) were recently proposed, but few of them robustly predict clinical outcomes. While mutation and expression signature of protein-coding genes were used in previous molecular subtyping methods, the noncoding genome in GC remains largely unexplored. Here, we developed the fast long-noncoding RNA analysis (FLORA) method to study RNA sequencing data of GC cases, and prioritized tumor-specific long-noncoding RNAs (lncRNAs) by integrating clinical and multi-omic data. We uncovered 1235 tumor-specific lncRNAs, based on which three subtypes were identified. The lncRNA-based subtype 3 (L3) represented a subgroup of intestinal GC with worse survival, characterized by prevalent TP53 mutations, chromatin instability, hypomethylation, and over-expression of oncogenic lncRNAs. In contrast, the lncRNA-based subtype 1 (L1) has the best survival outcome, while LINC01614 expression further segregated a subgroup of L1 cases with worse survival and increased chance of developing distal metastasis. We demonstrated that LINC01614 over-expression is an independent prognostic factor in L1 and network-based functional prediction implicated its relevance to cell migration. Over-expression and CRISPR-Cas9-guided knockout experiments further validated the functions of LINC01614 in promoting GC cell growth and migration. Altogether, we proposed a lncRNA-based molecular subtype of GC that robustly predicts patient survival and validated LINC01614 as an oncogenic lncRNA that promotes GC proliferation and migration.

scholarly journals Transient increase in circulating gamma/delta T cells during Plasmodium vivax malarial paroxysms.

1994 ◽  
Vol 179 (1) ◽  
pp. 311-315 ◽  
Author(s):  
M K Perera ◽  
R Carter ◽  
R Goonewardene ◽  
K N Mendis
Keyword(s):  
T Cells ◽  
Plasmodium Vivax ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Gastrointestinal Symptoms ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Endemic Region ◽  
Gastrointestinal Pathology

The percentage of peripheral blood mononuclear cells (PBMC) bearing the CD3+ phenotype and the alpha/beta and gamma/delta T cell receptors (TCR) in PBMC were examined in Plasmodium vivax malaria patients and convalescents. The cells were labeled with monoclonal antibodies, stained with either fluorescence or phycoerythrin, and examined by ultraviolet (UV) microscopy. A highly significant increase in both the proportion and the absolute numbers of gamma/delta T cells (p &lt; 0.005 and &lt; 0.001, respectively, Student's t test) was observed in nonimmune P. vivax patients during clinical paroxysms compared to nonmalarial controls. These T cells, which normally constitute not more than 3-5% of PBMC, constituted &lt; or = to 30% of PBMC during paroxysms in these nonimmune patients in whom the clinical symptoms were severe. A less significant increase of gamma/delta T cells were also observed in these nonimmune patients during infection, between paroxysms and during convalescence. In contrast, in an age-matched group of semi-immune patients resident in a malaria-endemic region of the country, in whom the clinical disease was comparatively mild, there was no increase in gamma/delta T cells either during infection, even during paroxysms, or convalescence. The severity of disease symptoms in patients as measured by a clinical score correlated positively with the proportion of gamma/delta T cells in peripheral blood (r = 0.53, p &lt; 0.01), the most significant correlation being found between the prevalence and severity of gastrointestinal symptoms, nausea, anorexia, and vomiting, and the proportion of gamma/delta T cells (r = 0.49, p = 0.002). These findings suggest that gamma/delta T cells have a role to play in the pathogenesis of malaria, possibly in the general constitutional disturbances and particularly in gastrointestinal pathology in malaria.

Peripheral blood leukocyte distribution and body mass index are associated with the methylation pattern of the androgen receptor promoter

Endocrine ◽  
2009 ◽  
Vol 35 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Sofia Movérare-Skrtic ◽  
Dan Mellström ◽  
Liesbeth Vandenput ◽  
Mathias Ehrich ◽  
Claes Ohlsson
Keyword(s):  
Body Mass Index ◽  
Androgen Receptor ◽  
Body Mass ◽  
Peripheral Blood ◽  
Peripheral Blood Leukocyte ◽  
Methylation Pattern ◽  
Blood Leukocyte

The Long Road to Understanding RNAPII Transcription Initiation and Related Syndromes

2021 ◽  
Vol 90 (1) ◽  
pp. 193-219
Author(s):  
Emmanuel Compe ◽  
Jean-Marc Egly
Keyword(s):  
Transcription Factors ◽  
Rna Polymerase Ii ◽  
Chromatin Remodeling ◽  
Transcription Initiation ◽  
Rna Synthesis ◽  
Regulatory Elements ◽  
Initiation Mechanism ◽  
Protein Coding ◽  
Core Promoters ◽  
General Transcription Factors

In eukaryotes, transcription of protein-coding genes requires the assembly at core promoters of a large preinitiation machinery containing RNA polymerase II (RNAPII) and general transcription factors (GTFs). Transcription is potentiated by regulatory elements called enhancers, which are recognized by specific DNA-binding transcription factors that recruit cofactors and convey, following chromatin remodeling, the activating cues to the preinitiation complex. This review summarizes nearly five decades of work on transcription initiation by describing the sequential recruitment of diverse molecular players including the GTFs, the Mediator complex, and DNA repair factors that support RNAPII to enable RNA synthesis. The elucidation of the transcription initiation mechanism has greatly benefited from the study of altered transcription components associated with human diseases that could be considered transcription syndromes.

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