Differential long non-coding RNA expression profile and function analysis in primary Sjogren’s syndrome

Chen, Xiaochan; Cheng, Qi; Du, Yan; Liu, Lei; Wu, Huaxiang

doi:10.1186/s12865-021-00439-3

Cited by 16 publications

(15 citation statements)

References 33 publications

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“…18 Transcriptome profiling studies have identified numerous differentially expressed (DE) lncRNAs in autoimmune diseases, including SjD. [19][20][21][22][23][24][25] These and similar studies applied expression correlation analyses with protein-coding RNAs (pcRNAs) to gain insights into the molecular roles of DE lncRNAs, but precise functional mechanisms remain undefined for many of the ~150 000 reported lncRNAs in the NONCODE database ( noncode. org).…”

Section: What This Study Addsmentioning

confidence: 99%

Dysregulated long non-coding RNA in Sjögren’s disease impacts both interferon and adaptive immune responses

Joachims

Khatri

et al. 2022

RMD Open

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ObjectiveSjögren’s disease (SjD) is an autoimmune disease characterised by inflammatory destruction of exocrine glands. Patients with autoantibodies to Ro/SSA (SjDRo+) exhibit more severe disease. Long non-coding RNAs (lncRNAs) are a functionally diverse class of non-protein-coding RNAs whose role in autoimmune disease pathology has not been well characterised.MethodsWhole blood RNA-sequencing (RNA-seq) was performed on SjD cases (n=23 Ro/SSA negative (SjDRo−); n=27 Ro/SSA positive (SjDRo+) and healthy controls (HCs; n=27). Bioinformatics and pathway analyses of differentially expressed (DE) transcripts (log2fold change ≥2 or ≤0.5; padj<0.05) were used to predict lncRNA function.LINC01871was characterised by RNA-seq analyses of HSB-2 cells with CRISPR-targetedLINC01871deletion (LINC01871−/−) and in vitro stimulation assays.ResultsWhole blood RNA-seq revealed autoantibody-specific transcription profiles and disproportionate downregulation of DE transcripts in SjD cases relative to HCs. Sixteen DE lncRNAs exhibited correlated expression with the interferon (IFN)-regulated gene,RSAD2, in SjDRo+(r≥0.65 or ≤−0.6); four antisense lncRNAs exhibited IFN-regulated expression in immune cell lines.LINC01871was upregulated in all SjD cases. RNA-seq and pathway analyses ofLINC01871−/−cells implicated roles in cytotoxic function, differentiation and IFNγ induction.LINC01871was induced by IFNγ in a myeloid cell line and regulated by calcineurin/NFAT pathway and T cell receptor (TCR) signalling in primary human T cells.ConclusionLINC01871influences expression of many immune cell genes and growth factors, is IFNγ inducible, and regulated by calcineurin signalling and TCR ligand engagement. AlteredLINC01871expression may influence the dysregulated T cell inflammatory pathways implicated in SjD.

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Section: What This Study Addsmentioning

confidence: 99%

Dysregulated long non-coding RNA in Sjögren’s disease impacts both interferon and adaptive immune responses

Joachims

Khatri

et al. 2022

RMD Open

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“…Interestingly, the lncR-NAs expression profile in PBMCs from pSS (INC00426, TPTEP1-202, CY-TOR, NRIR, and BISPR) correlated with the ESSDAI score and serum levels of IgG, C-reactive protein, and C4 complement (25). Other lncRNAs such as GABPB1-AS1 and PSMA3-AS1 are upregulated in PBMCs of pSS patients, and GABPB1-AS1 expression levels are positively correlated with IgG levels and percentage of B cells in pSS patients (26).…”

Section: Discussionmentioning

confidence: 97%

Interferon-alpha regulates expression of lncRNA MALAT1 and interferon-stimulated genes, as well as chemokine production, in primary Sjögren's syndrome

Amezcua-Guerra

Sánchez‐Muñoz

Pichardo-Ontiveros

et al. 2022

Clinical and Experimental Rheumatology

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ObjectiveThis study aimed to explore the contribution of interferon-alpha (IFN-α) to MALAT1 expression in primarySjögren's syndrome (pSS). Methods Peripheral blood mononuclear cells (PBMC) from pSS patients and healthy blood donors were stimulated with recombinant human IFN-α, and the expression levels of MALAT1 and several interferon-stimulated genes (ISGs) weremeasured by RT-PCR, while supernatant levels of interferon-regulated chemokines were measured using multiplex cytokine immunobead assay. ResultsIn this work, we found that MALAT1 expression levels were increased in IFN-α-stimulated PBMC from pSS patients and healthy controls. As expected, ISG expression levels and interferon-regulated chemokine secretion levels were higher after IFN-α stimulation. However, the fold-change values for ISG15, Ly6E, OAS1, and OASL expression levels were higher in cells from pSS patients than in controls. Similarly, PBMC from pSS patients produced higher concentrations of chemokines than those from healthy controls after IFN-α stimulation. Conclusion Our data provide insights into the abnormal IFN-α-mediated regulation of the lncRNA MALAT1 in pSS. Based on an unusually high capacity of PBMC to express ISG and to produce interferon-responsive chemokines,it is likely that targeted therapies to block these molecules may be of benefit to patients with pSS.

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“…Due to the complex pathogenesis and unclear pathophysiological mechanism of UC, the current clinical treatment has mainly focused on alleviating the symptoms ( Sarvestani et al, 2021 ; Ungaro et al, 2017 ). CeRNA cross-talk, mediated by miRNA in complex ceRNA networks, and the interactions between miRNA and lncRNA have been shown to play critical roles in the pathogenesis of various immune disorders ( Chen et al, 2021 ; Salmena et al, 2011 ; Song et al, 2021 ; Thomson and Dinger, 2016 ; Wu et al, 2021 ; Zhang Y et al, 2020 ). Studies have shown that lncRNA- ITSN1-2 acts as a competing endogenous RNA for IL-23R via sponging miR-125a , and lncRNA meg3 serves as a competing RNA for IL-10 via sponging miR-98-5p in IBD ( Nie and Zhao, 2020 ; Wang Y et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…LncRNAs, miRNA molecular “sponges,” can indirectly modulate gene expression through their ability to compete and sequester miRNAs, thereby inhibiting the miRNA-mediated suppression of target mRNAs ( Salmena et al, 2011 ). In the current research, ceRNA has been closely related to immune diseases, such as rheumatoid arthritis (RA), Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) ( Chen et al, 2021 ; Song et al, 2021 ; Wu et al, 2021 ; Zhang Y et al, 2020 ). Similarly, ceRNA has also been recently identified as one of the key mechanisms involved in the development of IBD ( Nie and Zhao, 2020 ; Liu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Construction, bioinformatics analysis, and validation of competitive endogenous RNA networks in ulcerative colitis

et al. 2022

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Background: Ulcerative colitis (UC) is a common chronic disease of the digestive system. Recently, competitive endogenous RNAs (ceRNAs) have been increasingly used to reveal key mechanisms for the pathogenesis and treatment of UC. However, the role of ceRNA in UC pathogenesis has not been fully clarified. This study aimed to explore the mechanism of the lncRNA-miRNA-mRNA ceRNA network in UC and identify potential biomarkers and therapeutic targets.Materials and Methods: An integrative analysis of mRNA, microRNA (miRNA), and long non-coding RNA (lncRNA) files downloaded from the Gene Expression Omnibus (GEO) was performed. Differentially expressed mRNA (DE-mRNAs), miRNA (DE-miRNAs), and lncRNA (DE-lncRNAs) were investigated between the normal and UC groups by the limma package. A weighted correlation network analysis (WGCNA) was used to identify the relative model for constructing the ceRNA network, and, concurrently, miRWalk and DIANA-LncBase databases were used for target prediction. Consecutively, the Gene Ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway, and Reactome pathway enrichment analyses, protein-protein interaction (PPI) network, Cytohubba, and ClueGO were performed to identify hub genes. Additionally, we examined the immune infiltration characteristics of UC and the correlation between hub genes and immune cells using the immuCellAI database. Finally, the expression of potential biomarkers of ceRNA was validated via qRT-PCR in an experimental UC model induced by dextran sulfate sodium (DSS).Result: The ceRNA network was constructed by combining four mRNAs, two miRNAs, and two lncRNAs, and the receiver operating characteristic (ROC) analysis showed that two mRNAs (CTLA4 and STAT1) had high diagnostic accuracy (area under the curve [AUC] > 0.9). Furthermore, CTLA4 up-regulation was positively correlated with the infiltration of immune cells. Finally, as a result of this DSS-induced experimental UC model, CTLA4, MIAT, and several associate genes expression were consistent with the results of previous bioinformatics analysis, which proved our hypothesis.Conclusion: The investigation of the ceRNA network in this study could provide insight into UC pathogenesis. CTLA4, which has immune-related properties, can be a potential biomarker in UC, and MIAT/miR-422a/CTLA4 ceRNA networks may play important roles in UC.

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Differential long non-coding RNA expression profile and function analysis in primary Sjogren’s syndrome

Cited by 16 publications

References 33 publications

Dysregulated long non-coding RNA in Sjögren’s disease impacts both interferon and adaptive immune responses

Dysregulated long non-coding RNA in Sjögren’s disease impacts both interferon and adaptive immune responses

Interferon-alpha regulates expression of lncRNA MALAT1 and interferon-stimulated genes, as well as chemokine production, in primary Sjögren's syndrome

Construction, bioinformatics analysis, and validation of competitive endogenous RNA networks in ulcerative colitis

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