scholarly journals Integrated Transcriptome Profiling Revealed That Elevated Long Non-Coding RNA-AC007278.2 Expression Repressed CCR7 Transcription in Systemic Lupus Erythematosus

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi You ◽  
Xingwang Zhao ◽  
Yaguang Wu ◽  
Jiangming Mao ◽  
Lan Ge ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Jurkat Cells ◽  
Luciferase Reporter ◽  
T Helper ◽  
Systemic Lupus ◽  
Non Coding Rna ◽  
Gene Assay ◽  
Long Non Coding Rna

PurposeSystemic lupus erythematosus (SLE) is a serious autoimmune disease. Its molecular pathogenesis, especially the long non-coding RNA (lncRNA) function, remains unclear. We want to investigate the lncRNA dysregulation profile and their molecular mechanisms in SLE.MethodsIn this study, we analyzed the transcriptome profiles (RNA-seq) of peripheral blood mononuclear cells (PBMCs) from SLE patients and two published transcriptome datasets to explore lncRNA profiles. The differentially expressed lncRNAs were confirmed by quantitative real-time PCR in another set of female patients. We constructed the lncRNA-mRNA regulatory networks by performing weighted gene co-expression network analysis (WGCNA). Dysregulated lncRNA AC007278.2 was repressed by short hairpin RNA (shRNA) in Jurkat cells. Dual-luciferase reporter gene assay was performed to investigate the regulatory mechanism of AC007278.2 on target gene CCR7.ResultsWe observed dominant up-regulation of transcripts, including mRNAs and lncRNAs, in SLE patients. By WGCNA method, we identified three modules that were highly related to SLE. We then focused on one lncRNA, AC007278.2, with a T-helper 1 lineage-specific expression pattern. We observed consistently higher AC007278.2 expression in SLE patients. Co-expression network revealed that AC007278.2 participated in the innate immune response and inflammatory bowel disease pathways. By knocking down AC007278.2 expression, we found that AC007278.2 could regulate the expression of inflammatory and cytokine stimulus response-related genes, including CCR7, AZU1, and TNIP3. AC007278.2 inhibits the functional CCR7 promoter to repress its transcription, thereby regulating autoimmunity and follicular T-helper cell differentiation.ConclusionIn summary, our study indicated the important regulatory role of lncRNAs in SLE. AC007278.2 may be treated as a novel biomarker for SLE diagnosis and treatment.

scholarly journals POS0416 NOVEL LONG NON-CODING RNA EXPRESSION PROFILE OF PERIPHERAL BLOOD MONOUCLEAR CELL REVEALED POTENTIAL BIOMARKERS AND REGULATORY MECHANISM IN SYSTEMIC LUPUS ERYTHEMATOSUS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 437.1-437
Author(s):  
Q. Cheng ◽  
M. Chen ◽  
X. Chen ◽  
X. Chen ◽  
H. Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Transcriptome Sequencing ◽  
Regulatory Mechanism ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Transcriptome Level

Background:Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease, usually involving multiple systems of the whole body (1). A variety of factors can affect SLE, such as genetic, environmental, immunoregulatory, hormonal and epigenetic (2). Long non-coding RNA is a type of RNA greater than 200 nucleotides that does not encode proteins. With the development of research, lncRNA gradually becomes the key regulator of gene expression in the immune system (3). Studies have shown that several lncRNAs, such as NEAT1 and GAS5 are dysregulated in SLE and are involved in the pathogenesis of SLE (4,5). These results suggest that lncRNA can be used as a potential biomarker for disease diagnosis and treatment. However, our current understanding of SLE related lncRNAS is still limited.Objectives:The purpose of this study was to find new lncRNAs in peripheral blood monouclear cells of SLE patients by transcriptome sequencing and explore their potential as biomarkers and their correlation with clinical features.Methods:Transcriptome sequencing was used to screen differentially expressed lncRNAs (DELs) and mRNAs (DEMs). DAVID and WebGestalt were used to perform enrichment analysis. Cytoscape was used to constructed protein-protein network, co-expression network and competitive endogenous RNA network to reveal the regulatory mechanism of lncRNAs in transcriptome level. The expression of these selected lncRNAs in SLE patients and healthy controls were verified by qPCR.Results:A toal of 1737 DELs and 4078 DEMs were identified between 5 SLE patients and 5 healthy controls. Most of upregulated genes were enriched in defense and immune response, while downregulated genes were mainly enriched in SLE related pathways. Topology network analysis reveal the regulatory mechanism of lncRNAs in transcriptome level including directly acting on mRNA or indirectly affecting gene expression after acting on miRNA. Ten lncRNAs and eight genes was verified by qPCR in bigger samples including 77 SLE patients and 25 healthy controls. LncRNA NONHSAT101022.2 was significantly downregulated in SLE patients (p=0.001) and the expression of NONHSAT101022.2 showed a significant negative correlation with SLE disease activity index (SLEDAI, r=-0.3592, p=0.0013).Conclusion:In this work, we identified a large number of mRNAs and novel lncRNAs by transcriptome sequence. The function and regulatory mechanism of these lncRNAs were analyzed by bioinformatics methods. LncRNA NONHSAT101022.2 is significantly downregulated in SLE patients and significantly related to the activity and severity of disease. Additionally, we put forward that NONHSAT101022.2 may enhance the signal transduction of β2-AR by cis-regulating its target gene, LMBRD2, which induces NK cells to produce high levels of IFN-γ, thereby exacerbating SLE.References:[1]Carter EE, Barr SG, Clarke AE. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol. 2016;12(10):605-20.[2]Han EC. Systemic lupus erythematosus. N Engl J Med. 2012;366(6):573-4; author reply.[3]Chen YG, Satpathy AT, Chang HY. Gene regulation in the immune system by long noncoding RNAs. Nat Immunol. 2017;18(9):962-72.[4]Zhang F, Wu L, Qian J, Qu B, Xia S, La T, et al. Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. Journal of autoimmunity. 2016;75:96-104.[5]Liu Q, Deng Y, Li C, Xie H, Liu Q, Ming S, et al. LncRNA GAS5 suppresses CD4(+) T cell activation by upregulating E4BP4 via inhibiting miR-92a-3p in systemic lupus erythematosus. Immunol Lett. 2020;227:41-7.Disclosure of Interests:None declared

scholarly journals Targeting Intra-Pulmonary P53-Dependent Long Non-Coding RNA Expression as a Therapeutic Intervention for Systemic Lupus Erythematosus-Associated Diffuse Alveolar Hemorrhage

2021 ◽  
Vol 22 (13) ◽  
pp. 6948
Author(s):  
Yi-Cheng Chen ◽  
Yu-Chi Chou ◽  
Yu-Tung Hsieh ◽  
Pin-Yu Kuo ◽  
Mei-Lin Yang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Cell Apoptosis ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Epithelial Cells ◽  
Alveolar Hemorrhage ◽  
Systemic Lupus ◽  
Lncrna Expression ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Diffuse alveolar hemorrhage (DAH) in systemic lupus erythematosus (SLE) is associated with significant mortality, requiring a thorough understanding of its complex mechanisms to develop novel therapeutics for disease control. Activated p53-dependent apoptosis with dysregulated long non-coding RNA (lncRNA) expression is involved in the SLE pathogenesis and correlated with clinical activity. We examined the expression of apoptosis-related p53-dependent lncRNA, including H19, HOTAIR and lincRNA-p21 in SLE-associated DAH patients. Increased lincRNA-p21 levels were detected in circulating mononuclear cells, mainly in CD4+ and CD14+ cells. Higher expression of p53, lincRNA-p21 and cell apoptosis was identified in lung tissues. Lentivirus-based short hairpin RNA (shRNA)-transduced stable transfectants were created for examining the targeting efficacy in lncRNA. Under pristane stimulation, alveolar epithelial cells had increased p53, lincRNA-p21 and downstream Bax levels with elevated apoptotic ratios. After pristane injection, C57/BL6 mice developed DAH with increased pulmonary expression of p53, lincRNA-p21 and cell apoptosis. Intra-pulmonary delivery of shRNA targeting lincRNA-p21 reduced hemorrhage frequencies and improved anemia status through decreasing Bax expression and cell apoptosis. Our findings demonstrate increased p53-dependent lncRNA expression with accelerated cell apoptosis in the lungs of SLE-associated DAH patients, and show the therapeutic potential of targeting intra-pulmonary lncRNA expression in a pristane-induced model of DAH.

scholarly journals Circular RNA circLOC101928570 Suppress Systemic Lupus Erythematosus Progression Via Targeting the miR-150/c-myb Axis

2021 ◽  
Author(s):  
Xingwang Zhao ◽  
Longlong Zhang ◽  
Juan Wang ◽  
Zhiqiang Song ◽  
Bing Ni ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Transcriptional Level ◽  
Systemic Lupus ◽  
Potential Biomarker ◽  
Repressive Effect

Abstract Background: Accumulating evidence supports the implication of circRNAs in systemic lupus erythematosus (SLE). however, little is known about their the detailed mechanisms and the roles of circRNAs in the pathogenesis of SLE.Methods: Quantitative real time-PCR (qRT-PCR) was used to determine the levels of circLOC101928570 and miR-150 in peripheral blood mononuclear cells (PBMCs) of SLE. Overexpression and knockdown experiments were conducted to assess the effects of circLOC101928570. Fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), luciferase reporter assays, western blot, flow cytometry analysis and enzyme-linked immunosorbent assay (ELISA) were used to investigate the molecular mechanisms underlying the function of circLOC101928570. Results: The results showed that the level of circLOC101928570 was significantly down-regulated in SLE and correlated with systemic lupus erythematosus disease activity index (SLEDAI). Functionally, circLOC101928570 acted as a miR-150 sponge to relieve the repressive effect on its target c-myb, which modulates the activation of immune inflammatory responses. CircLOC101928570 knockdown enhanced apoptosis. Moreover, circLOC101928570 promote the transcriptional level of IL2RA through directly regulate miR-150/c-myb axis. Conclusion: Overall, our findings demonstrated that circLOC101928570 played a critical role in SLE. The down-expression of circLOC101928570 suppressed SLE progression through miR-150/c-myb/IL2RA axis. Our findings identified that circLOC101928570 serve as a potential biomarker for the diagnosis and therapy of SLE.

Myocardial Infarction in Systemic Lupus Erythematosus – the Sex Specific Risk Profile

2020 ◽  
Vol 26 ◽  
Author(s):  
Marija Vavlukis ◽  
Daniela Pop-Gjorceva ◽  
Lidija Poposka ◽  
Emilija Sandevska ◽  
Sasko Kedev
Keyword(s):  
Myocardial Infarction ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Risk ◽  
Coronary Artery ◽  
Young Women ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Clinical Presentation ◽  
Systemic Lupus ◽  
Antiinflammatory Therapy

Background: Accelerated atherosclerosis is widely present in patients with systemic lupus erythematosus. Objective: The aim of this review is to analyze the relationship between systemic lupus erythematosus and cardiovascular diseases, with the emphasis on acute myocardial infarction. Results: Various molecular mechanisms triggered by infection/inflammation are responsible for endothelial dysfunction and development of atherosclerosis at an earlier age. Contributing factor is the cumulative effect of traditional cardiovascular risk factors interaction with disease related characteristics. Myocardial infarction rates are 2- to 10-fold higher compared to the general population. Young women have the highest relative risk, however, men carry at least 3- fold higher risk than women. Coronary involvement varies from normal coronary artery with thrombosis, coronary microartery vasculitis, coronary arteritis, and coronary atherosclerosis. Typical clinical presentation is observed in men and older women, while atypical is more frequent in young women. Treatment is guided by the underlying mechanism, engaging invasive procedures alone, or accompanied with immunosuppressive and/or antiinflammatory therapy. There are significant gender differences in pathophysiology and clinical presentation. However, they receive the same therapeutic treatments. Conclusion: Systemic lupus erythematosus is a major contributor to atherosclerotic and non-atherosclerotic mechanisms involved in the development of myocardial infarction, which should be taken into account during therapeutic treatment. Although Systemic lupus erythematosus per se is a “female” disease, males are at increased cardiovascular risk and worse outcome. Method: We conducted a literature review through PubMed and Cochrane, using key words: SLE, atherosclerosis, atherothrombosis, coronary artery disease, myocardial infarction, prognosis, sex specifics.

Detection and Functional Evaluation of −262A/T and −188A/G Polymorphisms of SLAM Gene in Patients with Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (11) ◽  
pp. 2268-2272 ◽  
Author(s):  
YI YOU ◽  
ZHE WANG ◽  
GUO-HONG DENG ◽  
YI LIU ◽  
FEI HAO
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Gene Promoter ◽  
Chinese Patients ◽  
Luciferase Reporter ◽  
Functional Evaluation ◽  
Reporter System ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear

Objective.Signaling lymphocytic activation molecule (SLAM) has been related to the pathology of systemic lupus erythematosus (SLE) through regulation of T cell-dependent humoral immune responses. We investigated the functional associations of the −262A/T and −188A/G polymorphisms of SLAM in Chinese patients with SLE.Methods.Genotyping of −262A/T (rs2295614) and −188A/G (rs2295613) in SLAM was carried out in 248 cases and 278 controls. Promoter activities of haplotypes on the SLAM gene were evaluated with the dual-luciferase reporter system. The mRNA expressions of SLAM on peripheral blood mononuclear cells (PBMC) of SLE patients with different genotypes were determined by real-time polymerase chain reaction.Results.Frequencies of −262A allele and −188G allele were significantly higher in SLE patients than in controls. Haplotype analysis and multifactorial logistic regression analysis showed that individuals with the AG/AG haplotype had increased susceptibility to SLE (p = 0.002, OR 1.478, 95% CI 1.152–1.897). In response to PHA stimulation, the SLAM mRNA expression on PBMC of SLE patients was significantly higher in −262A-188G haplotype homozygotes compared with −262A-188G heterozygotes and individuals with other genotypes.Conclusion.Our findings suggest that −262A-188G haplotype in the SLAM gene promoter contributes to the risk of SLE by increasing the expression of SLAM.

scholarly journals The gene expression of type 17 T-helper cell-related cytokines in the urinary sediment of patients with systemic lupus erythematosus

Rheumatology ◽  
2009 ◽  
Vol 48 (12) ◽  
pp. 1491-1497 ◽  
Author(s):  
B. C.-H. Kwan ◽  
L.-S. Tam ◽  
K.-B. Lai ◽  
F. M.-M. Lai ◽  
E. K.-M. Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Systemic Lupus ◽  
Urinary Sediment
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