LncRNA of human Fibroblast-like synoviocytes of rheumatoid arthritis and osteoarthritis
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ABSTRACT: To further development of lncRNA expression differences, we have employed whole lncRNA microarray expression profiling as a discovery platform to identify lncRNA with the potential to distinguish
Project description:This study was to investigate the lncRNA expression profiles in synovium tissues of rheumatoid arthritis (RA) patients by RNA sequencing, and to evaluate the clinical values of dysregulated lncRNAs in RA diagnosis and monitoring.
Project description:LncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in fibroblast-like synoviocytes from rheumatoid arthritis patients compared with fibroblast-like synoviocytes from trauma patients. Fibroblast-like synoviocytes were isolated from synovial tissues. LncRNA and mRNA microarrays were performed using fibroblast-like synoviocytes at passage 3.
Project description:Fibroblast-like synoviocytes (FLSs) are critical for synovial aggressiveness and joint destruction in rheumatoid arthritis (RA).The role and expression patterns of long noncoding RNAs (lncRNAs) in RA are largely unknown. We performed lncRNA and mRNA microarrays to identify differentially expressed lncRNAs and mRNAs in fibroblast-like synoviocytes from rheumatoid arthritis patients compared with fibroblast-like synoviocytes from trauma patients.
Project description:Objective: Tripterygium is a traditional Chinese medicine which has widely been used in the treatment of rheumatic disease. (5R)-5-hydroxytriptolide (LLDT-8) is an extracted compound from Tripterygium, which has been showed lower cytotoxicity and relatively higher immunosuppressive activity. However, the knowledge on its genomic impact is still limited. Methods: The purpose of our study was to assess the effects of LLDT-8 on transcriptome including mRNAs and lncRNAs in rheumatoid arthritis fibroblast-like synoviocytes cell by a custom genome-wide microarray assay. Results: Our work showed that 394 significantly differentially expressed gene including 281 significantly down-regulated and 113 significantly up-regulated after the treatment of LLDT-8. Also, KEGG pathway analysis showed 20 pathways were significantly enriched (P-value <0.05, FDR correction). Morever, the top 4 enriched pathway were significant relevant to Immune reaction, including cytokine-cytokine receptor interaction (P-value=4.61×10-13), rheumatoid arthritis (P-value=1.90×10-6), chemokine signaling pathway (P-value=1.01×10-5) and TNF signaling pathway (P-value=2.79×10-4). Furthermore, we identified 1,716 highly correlated lncRNA-mRNA pairs from the selected top lncRNA and mRNA, and 70 pairs of them were located in the same Chromosome. Conclusion: The results indicated that the LLDT-8 would mainly influence the RA cells in the process of immune network regulation.
Project description:LncRNA NEAT1 functions as an oncogene in multiple human cancers. However, its expression and role in fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) remain unclear. Thus, we investigated the expression of NEAT1 in synovial tissues and FLSs in RA, to determine its role in the development of RA. Quantitative real-time polymerase chain reaction was used to measure the expression of NEAT1. FLS proliferation was evaluated using cell proliferation assays. Flow cytometry was used to analyze cell cycle progression and apoptosis in FLSs. Binding between NEAT1 and miR-410-3p was demonstrated by dual-luciferase assays. We found that NEAT1 was upregulated in synovial tissues and FLSs in RA. Upregulation of NEAT1 promoted cell proliferation, induced S-to G2/M phase transition, and suppressed apoptosis in RA FLSs. NEAT1 directly bound to and negatively modulated miR-410-3p expression, while positively regulating YinYang 1(YY1; a miR-410-3p target). Inhibiting miR-410-3p and upregulating YY1 partially restored the inhibitory role in cell viability induced by the depletion of NEAT1 in RA FLSs. Besides pro-proliferative and anti-apoptotic roles, upregulation of NEAT1 promoted migration, invasion, and inflammatory cytokines secretion in RA FLSs. Taken together, our results suggest that the NEAT1 may serve as a novel diagnostic and therapeutic target for patients with RA.
Project description:Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells and are associated with active enhancers and promoters and specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with "Huntington's Disease Signaling" identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.
Project description:To further development of MG-related lncRNA expression differences, we have employed whole lncRNA microarray expression profiling as a discovery platform to identify MG-related lncRNA with the potential to distinguish MG.
Project description:LncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in fibroblast-like synoviocytes from rheumatoid arthritis patients compared with fibroblast-like synoviocytes from trauma patients.
Project description:Fibroblast-like synoviocyte (FLS) constitutes a major cell subset of rheumatoid arthritis (RA) joint. Dysregulation of microRNAs (miRNAs) contributes to FLS activation in the context of chronic inflammation. However, functional association of the miRNAs-targets relationships characterizing FLS phenotypes in RA has not been fully elucidated yet. Thus, we uncovered the novel miRNA-target interactions characterizing pathologic phenotypes of RA-FLS. We performed microarray analyses of miRNA in RA- and osteoarthritis (OA) FLS with or without interleukin-1β (IL-1β) stimulation. The miRNA-target prediction and network model-ing were performed using TargetScan and Cytoscape. Identified miRNA-target relationships and their cellular functions were validated in vitro.