scholarly journals Long Non-Coding RNA- Associated Competing Endogenous RNA Axes in T-Cells in Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hani Sabaie ◽  
Zoha Salkhordeh ◽  
Mohammad Reza Asadi ◽  
Soudeh Ghafouri-Fard ◽  
Nazanin Amirinejad ◽  
...  

Multiple sclerosis (MS) is an immune-mediated demyelinating and degenerative disease with unknown etiology. Inappropriate response of T-cells to myelin antigens has an essential role in the pathophysiology of MS. The clinical and pathophysiological complications of MS necessitate identification of potential molecular targets to understand the pathogenic events of MS. Since the functions and regulatory mechanisms of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in MS are yet uncertain, we conducted a bioinformatics analysis to explain the lncRNA-associated ceRNA axes to clarify molecular regulatory mechanisms involved in T-cells responses in MS. Two microarray datasets of peripheral blood T-cell from subjects with relapsing-remitting MS and matched controls containing data about miRNAs (GSE43590), mRNAs and lncRNAs (GSE43591) were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs (DEmiRNAs), mRNAs (DEmRNAs), and lncRNAs (DElncRNAs) were identified by the limma package of the R software. Protein-protein interaction (PPI) network and module were developed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and the Molecular Complex Detection (MCODE) Cytoscape plugin, respectively. Using DIANA-LncBase and miRTarBase, the lncRNA-associated ceRNA axes was constructed. We conducted a Pearson correlation analysis and selected the positive correlations among the lncRNAs and mRNAs in the ceRNA axes. Lastly, DEmRNAs pathway enrichment was conducted by the Enrichr tool. A ceRNA regulatory relationship among Small nucleolar RNA host gene 1 (SNHG1), hsa-miR-197-3p, YOD1 deubiquitinase (YOD1) and zinc finger protein 101 (ZNF101) and downstream connected genes was identified. Pathway enrichment analysis showed that DEmRNAs were enriched in “Protein processing in endoplasmic reticulum” and “Herpes simplex virus 1 infection” pathways. To our knowledge, this would be the first report of a possible role of SNHG1/hsa-miR-197-3p/YOD1/ZNF101 axes in the pathogenesis of MS. This research remarks on the significance of ceRNAs and prepares new perceptions for discovering the molecular mechanism of MS.

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Shao-Mei Wang ◽  
Ze-Qiang Sun ◽  
Hong-Yun Li ◽  
Jin Wang ◽  
Qing-Yong Liu

Objective. The objective of this work is to identify dysregulated genes and pathways of ccRCC temporally according to systematic tracking of the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks.Methods. Firstly, normal and ccRCC PPI network were inferred and reweighted based on Pearson correlation coefficient (PCC). Then, we identified altered modules using maximum weight bipartite matching and ranked them in nonincreasing order. Finally, gene compositions of altered modules were analyzed, and pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test.Results. We obtained 136, 576, 693, and 531 disrupted modules of ccRCC stages I, II, III, and IV, respectively. Gene composition analyses of altered modules revealed that there were 56 common genes (such asMAPK1,CCNA2, andGSTM3) existing in the four stages. Besides pathway enrichment analysis identified 5 common pathways (glutathione metabolism, cell cycle, alanine, aspartate, and glutamate metabolism, arginine and proline metabolism, and metabolism of xenobiotics by cytochrome P450) across stages I, II, III, and IV.Conclusions. We successfully identified dysregulated genes and pathways of ccRCC in different stages, and these might be potential biological markers and processes for treatment and etiology mechanism in ccRCC.


2018 ◽  
Vol 78 (2) ◽  
pp. 270-277 ◽  
Author(s):  
Rodrigo Coutinho de Almeida ◽  
Yolande F M Ramos ◽  
Ahmed Mahfouz ◽  
Wouter den Hollander ◽  
Nico Lakenberg ◽  
...  

ObjectiveTo uncover the microRNA (miRNA) interactome of the osteoarthritis (OA) pathophysiological process in the cartilage.MethodsWe performed RNA sequencing in 130 samples (n=35 and n=30 pairs for messenger RNA (mRNA) and miRNA, respectively) on macroscopically preserved and lesioned OA cartilage from the same patient and performed differential expression (DE) analysis of miRNA and mRNAs. To build an OA-specific miRNA interactome, a prioritisation scheme was applied based on inverse Pearson’s correlations and inverse DE of miRNAs and mRNAs. Subsequently, these were filtered by those present in predicted (TargetScan/microT-CDS) and/or experimentally validated (miRTarBase/TarBase) public databases. Pathway enrichment analysis was applied to elucidate OA-related pathways likely mediated by miRNA regulatory mechanisms.ResultsWe found 142 miRNAs and 2387 mRNAs to be differentially expressed between lesioned and preserved OA articular cartilage. After applying prioritisation towards likely miRNA-mRNA targets, a regulatory network of 62 miRNAs targeting 238 mRNAs was created. Subsequent pathway enrichment analysis of these mRNAs (or genes) elucidated that genes within the ‘nervous system development’ are likely mediated by miRNA regulatory mechanisms (familywise error=8.4×10−5). Herein NTF3 encodes neurotrophin-3, which controls survival and differentiation of neurons and which is closely related to the nerve growth factor.ConclusionsBy an integrated approach of miRNA and mRNA sequencing data of OA cartilage, an OA miRNA interactome and related pathways were elucidated. Our functional data demonstrated interacting levels at which miRNA affects expression of genes in the cartilage and exemplified the complexity of functionally validating a network of genes that may be targeted by multiple miRNAs.


Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582091420
Author(s):  
Jinfeng Huang ◽  
Qi Wang ◽  
Zhenhua Qi ◽  
Shixiang Zhou ◽  
Meijuan Zhou ◽  
...  

Radiation biodosimeters are required urgently for fast and accurate evaluation of absorbed dose for irradiated individuals. Lipidomics has appeared as a credible technique for identification and quantification of lipid for researching biomarker of diseases. We performed a lipidomic profile on mice serum at time points of 6, 24, and 72 hours after 0, 2, 5.5, 7, and 8 Gy irradiation to select radiation-responsive lipids and conducted Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis to recognize the pathways and network changes. Then, Pearson correlation analysis was performed to evaluate the feasibility of radiation-responsive lipids to estimate radiation dose. Seven radiation-responsive lipids including PC (18:2/18:2), PC (18:0/18:2), Lyso PC 18:1, PC (18:0/20:4), SM (D18:0/24:1), PC (16:0/18:1), and Lyso PC 18:2 were identified in which glycerophospholipid metabolism presented as the most significant pathway, and they all presented good linear correlation with the irradiated dose. This study identified 7 radiation-responsive lipids in mice serum and certificate their feasibility of dose estimation as biodosimeters.


2013 ◽  
Vol 40 (12) ◽  
pp. 1256
Author(s):  
XiaoDong JIA ◽  
XiuJie CHEN ◽  
Xin WU ◽  
JianKai XU ◽  
FuJian TAN ◽  
...  

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qinghong Shi ◽  
Hanxin Yao

Abstract Background Our study aimed to investigate signature RNAs and their potential roles in type 1 diabetes mellitus (T1DM) using a competing endogenous RNA regulatory network analysis. Methods Expression profiles of GSE55100, deposited from peripheral blood mononuclear cells of 12 T1DM patients and 10 normal controls, were downloaded from the Gene Expression Omnibus to uncover differentially expressed long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs). The ceRNA regulatory network was constructed, then functional and pathway enrichment analysis was conducted. AT1DM-related ceRNA regulatory network was established based on the Human microRNA Disease Database to carry out pathway enrichment analysis. Meanwhile, the T1DM-related pathways were retrieved from the Comparative Toxicogenomics Database (CTD). Results In total, 847 mRNAs, 41 lncRNAs, and 38 miRNAs were significantly differentially expressed. The ceRNA regulatory network consisted of 12 lncRNAs, 10 miRNAs, and 24 mRNAs. Two miRNAs (hsa-miR-181a and hsa-miR-1275) were screened as T1DM-related miRNAs to build the T1DM-related ceRNA regulatory network, in which genes were considerably enriched in seven pathways. Moreover, three overlapping pathways, including the phosphatidylinositol signaling system (involving PIP4K2A, INPP4A, PIP4K2C, and CALM1); dopaminergic synapse (involving CALM1 and PPP2R5C); and the insulin signaling pathway (involving CBLB and CALM1) were revealed by comparing with T1DM-related pathways in the CTD, which involved four lncRNAs (LINC01278, TRG-AS1, MIAT, and GAS5-AS1). Conclusion The identified signature RNAs may serve as important regulators in the pathogenesis of T1DM.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shams Tabrez ◽  
Mohammed Razeeth Shait Mohammed ◽  
Nasimudeen R. Jabir ◽  
Mohammad Imran Khan

Abstract Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality around the world. Early diagnosis of CVD could provide the opportunity for sensible management and better clinical outcome along with the prevention of further progression of the disease. In the current study, we used an untargeted metabolomic approach to identify possible metabolite(s) that associate well with the CVD and could serve either as therapeutic target or disease-associated metabolite. We identified 26 rationally adjusted unique metabolites that were differentially present in the serum of CVD patients compared with healthy individuals, among them 15 were found to be statistically significant. Out of these metabolites, we identified some novel metabolites like UDP-l-rhamnose and N1-acetylspermidine that have not been reported to be linked with CVD directly. Further, we also found that some metabolites like ethanolamide, solanidine, dimethylarginine, N-acetyl-l-tyrosine, can act as a discriminator of CVD. Metabolites integrating pathway enrichment analysis showed enrichment of various important metabolic pathways like histidine metabolism, methyl histidine metabolism, carnitine synthesis, along with arginine and proline metabolism in CVD patients. Our study provides a great opportunity to understand the pathophysiological role and impact of the identified unique metabolites and can be extrapolated as specific CVD specific metabolites.


2017 ◽  
Vol 20 (1) ◽  
pp. 168-177 ◽  
Author(s):  
Qian Yang ◽  
Shuyuan Wang ◽  
Enyu Dai ◽  
Shunheng Zhou ◽  
Dianming Liu ◽  
...  

2021 ◽  
Author(s):  
Yong Liu ◽  
Sheng Nan Cui ◽  
Meng Yao Duan ◽  
Zhi Li Dou ◽  
Yi Zhen Li ◽  
...  

Abstract Background: The relationship between psoriasis and hepatitis C was previously controversial, so our purpose is to investigate this connection.Methods: We conducted a systematic review of the case-control, cross-sectional and cohort studies examining the association between psoriasis and hepatitis C in PubMed, EMBASE and Cochrane library databases and investigated the overlapping genes between psoriasis targets and hepatitis C targets using bioinformatics analysis. Based on overlapping genes and hub nodes, we also constructed the protein-protein interaction (PPI) network and module respectively, followed by the pathway enrichment analysis. Results: We included 11 publications that reported a total of 11 studies (8 cross-sectional and 3 case-control). The case–control and cross-sectional studies included 25,047 psoriasis patients and 4,091,631 controls in total. Psoriasis was associated with a significant increase of prevalent hepatitis C (OR 1.72; 95% confidence interval [CI] (1.17-2.52)). A total of 389 significant genes were common to both hepatitis C and psoriasis, which mainly involved IL6, TNF, IL10, ALB, STAT3 and CXCL8. The module and pathway enrichment analyses showed that the common genes had the potential to influence varieties of biological pathways, including the inflammatory response, cytokine activity, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, which play an important role in the pathogenesis of hepatitis C and psoriasis.Conclusion: Patients with psoriasis display increased prevalence of hepatitis C and the basic related mechanisms between hepatitis C and psoriasis had been preliminarily clarified.


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