Differential expression of circular RNAs in plasma exosomes from patients with ankylosing spondylitis

Zhang, Lele; Qu, Lin; Zhang, Yurong; Xu, Zhijiang; Tang, Huqiang

doi:10.1002/cbin.11760

Cited by 11 publications

(6 citation statements)

References 38 publications

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“…The miRNA content of exosomes has been found to differ from their parent cells, indicating that their cargo packaging is a selective process 19 20. Profiling plasma exosomal miRNAs hse already contributed to increased knowledge of the role of exosomes in the pathogenesis of AS 21–28…”

Section: Introductionmentioning

confidence: 99%

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis

et al. 2023

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IntroductionRecent advances in understanding the biology of ankylosing spondylitis (AS) using innovative genomic and proteomic approaches offer the opportunity to address current challenges in AS diagnosis and management. Altered expression of genes, microRNAs (miRNAs) or proteins may contribute to immune dysregulation and may play a significant role in the onset and persistence of inflammation in AS. The ability of exosomes to transport miRNAs across cells and alter the phenotype of recipient cells has implicated exosomes in perpetuating inflammation in AS. This study reports the first proteomic and miRNA profiling of plasma-derived exosomes in AS using comprehensive computational biology analysis.MethodsPlasma samples from patients with AS and healthy controls (HC) were isolated via ultracentrifugation and subjected to extracellular vesicle flow cytometry analysis to characterise exosome surface markers by a multiplex immunocapture assay. Cytokine profiling of plasma-derived exosomes and cell culture supernatants was performed. Next-generation sequencing was used to identify miRNA populations in exosomes enriched from plasma fractions. CD4+ T cells were sorted, and the frequency and proliferation of CD4+ T-cell subsets were analysed after treatment with AS-exosomes using flow cytometry.ResultsThe expression of exosome marker proteins CD63 and CD81 was elevated in the patients with AS compared with HC (q<0.05). Cytokine profiling in plasma-derived AS-exosomes demonstrated downregulation of interleukin (IL)-8 and IL-10 (q<0.05). AS-exosomes cocultured with HC CD4+ T cells induced significant upregulation of IFNα2 and IL-33 (q<0.05). Exosomes from patients with AS inhibited the proliferation of regulatory T cells (Treg), suggesting a mechanism for chronically activated T cells in this disease. Culture of CD4+ T cells from healthy individuals in the presence of AS-exosomes reduced the proliferation of FOXP3+ Treg cells and decreased the frequency of FOXP3+IRF4+ Treg cells. miRNA sequencing identified 24 differentially expressed miRNAs found in circulating exosomes of patients with AS compared with HC; 22 of which were upregulated and 2 were downregulated.ConclusionsIndividuals with AS have different immunological and genetic profiles, as determined by evaluating the exosomes of these patients. The inhibitory effect of exosomes on Treg in AS suggests a mechanism contributing to chronically activated T cells in this disease.

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Section: Introductionmentioning

confidence: 99%

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis

et al. 2023

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“…A signi cant proportion of circRNAs are concentrated in peripheral blood, peripheral blood mononuclear cells, platelets, plasma, spinal ligament tissues, and bone marrow-derived mesenchymal stem cells, indicating potential functions in spondyloarthritis. Broadly speaking, the dysregulation of circRNAs may have an impact on fundamental molecular mechanisms that are involved in the development of ankylosing spondylitis (AS) [24]. Therefore, a more profound comprehension of the role of circRNAs in JSpA is required.…”

Section: Discussionmentioning

confidence: 99%

Identifying circRNA-associated-ceRNA networks in juvenile spondyloarthropathies patients.

Wei

2023

Preprint

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Background Juvenile spondyloarthropathies (JSpA) are defined as a heterogeneous group of diseases that start before the age of 16. The study aimed to identify key genes and pathways that are influenced by circRNAs and to screen potential therapeutic agents for JSpA. The study likely involved the analysis of circRNA expression profiles, identification of circRNA-miRNA-mRNA regulatory networks, and functional annotation of differentially expressed genes. The results of the study may have provided insights into the molecular mechanisms underlying JSpA and potential therapeutic targets for this disease.Methods In this study, sequencing data of circRNA, miRNA, and mRNA were obtained from the GEO datasets. The data were then analyzed to identify candidates for constructing a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Functional enrichments of genes were performed using the DAVID database. A PPI network was constructed using the STRING database and visualized using Cytoscape software. The MCODE plugin app was used to explore hub genes in the PPI network. The expression changes in immune cells were assessed using the online CIBERSORT algorithm to obtain the proportion of various types of immune cells. Finally, the Connectivity Map L1000 platform was used to identify potential agents for JSpA treatment. Overall, this study aimed to provide a comprehensive understanding of the molecular mechanisms underlying JSpA and to identify potential therapeutic agents for this disease.Results A total of 225 differentially expressed circRNAs (DEcircRNAs), 23 differentially expressed miRNAs (DEmiRNAs) and 1324 differentially expressed mRNAs (DEmRNAs) were identified. We integrated 5 overlapped circRNAs, 7 miRNAs and 299 target mRNAs into a circRNA–miRNA–mRNA network. We next identified 10 hub genes based on the PPI network. KEGG pathway analysis revealed that the DEGs were mainly associated with JAK-STAT signal pathway. We found that neutrophils accounted for the majority of all infiltrating cells. In addition, we discovered several chemicals as potential treatment options for JSpA.Conclusions Through this bioinformatics analysis, we suggest a regulatory role for circRNAs in the pathogenesis and treatment of JSpA from the view of a competitive endogenous RNA (ceRNA) network.

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“…Moreover, NEAT1 has promoted the progression of RA by downregulating miR-144-3p and upregulating Rho-associated protein kinase 2 (ROCK2), suggesting that NEAT1 may be a potential biomarker and therapeutic target for RA [117]. The levels of exosomal circRNAs, like circ-0110797, circ-0097378, circ-0122309, circ-0058275, and circ-0008346 in AS, were significantly down-regulated compared with healthy donors, providing more optional biomarkers for the early diagnosis of AS [118].…”

Section: Autoimmune Diseasementioning

confidence: 99%

Perspective Chapter: Clinical Application of Exosome Components

Hou¹,

Li²,

Wang³

et al. 2023

Exosomes - Recent Advances From Bench to Bedside

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Exosomes belong to a subpopulation of EVs that carry different functional molecular cargoes, including proteins, nucleic acids, metabolites, and lipids. Notably, evidence has demonstrated that exosomes participate in bidirectional cell–cell communication and act as critical molecular vehicles in regulating numerous physiological and pathological processes. Since the specific contents within exosomes carry the information from their cells of origin, this property permits exosomes to act as valuable biomarkers. This chapter summarizes the potential use of exosome components in diagnosing, prognosis, or monitoring and treating multiple cancers and other non-neoplastic diseases. We also discuss the deficiency of basic applications, including the limitations of research methods and different research institutions and the differences generated by specimen sources. Thus, a better understanding of the problem of exosome detection may pave the way to promising exosome-based clinical applications.

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Differential expression of circular RNAs in plasma exosomes from patients with ankylosing spondylitis

Cited by 11 publications

References 38 publications

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis

Identifying circRNA-associated-ceRNA networks in juvenile spondyloarthropathies patients.

Perspective Chapter: Clinical Application of Exosome Components

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