Abstract
BackgroundCirculating RNA (circRNA) regulates various bioactivities in cells. A better understanding of the exosomal circRNA can provide novel insights into the pathogenesis and treatment of Graves’ disease (GD). We aimed to profile the differentially expressed circRNAs (DEcRs) in plasma exosomes of patients with GD and speculate and probe the functions of the DEcR by comprehensive bioinformatics analyses.MethodsSerum exosomes were isolated from five primary GD patients and five healthy controls via ultracentrifugation. After verification with transmission electron microscopy, exosome samples were subjected to microarray profiling using human circRNA microarrays. Two up-regulated and two down-regulated DEcRs were selected for validation in plasma exosomes from 20 GD and 20 healthy control participants using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The circRNA/microRNA/mRNA interaction network was then assembled and the analysis of the Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was utilized to predict the potential functions of the DEcR associated genes.ResultsThere were 15 DEcRs revealed in primary GD cases. The intronic circRNA hsa_circRNA_000102 was confirmed as an up-regulated component in plasma exosomes from patients with GD. The circRNA/microRNA/mRNA interaction network unveiled the most potential targeting microRNAs of hsa_circRNA_000102 and its associated genes. The functional analyses predicted involvement of hsa_circRNA_000102 associated genes in pathways of immune system activation, such as viral infection and interferon-beta signaling.Conclusionshsa_circRNA_000102 is a differentially up-regulated plasma exosomal circRNA in patients with GD. Our study highlights multiple pathways, particularly virus infection and interferon-beta signaling, for mediating immune activation in Graves’ disease.
Highlights
Circulating RNA regulates various bioactivities in cells
The concentration of plasma TRAb (TSH receptor antibodies, called thyroid-stimulating antibody (TSAb)), the specific thyroid autoantibody produced in Graves’ disease (GD) (29.49 ± 14.77 IU/L), was remarkably higher in GD patients than in healthy control subjects (0.55 ± 0.32 IU/L)
Our comprehensive bioinformatics analyses, including prediction of a Circulating RNA (circRNA)/microRNA/mRNA interaction network for hsa_circRNA_000102 and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations of hsa_circRNA_000102 associated genes, revealed potential pathways correlated to the pathogenesis of GD
Summary
A better understanding of the exosomal circRNA can provide novel insights into the pathogenesis and treatment of Graves’ disease (GD). We aimed to profile the differentially expressed circRNAs (DEcRs) in plasma exosomes of patients with GD and speculate and probe the functions of the DEcR by comprehensive bioinformatics analyses. GD is the most common cause of hyperthyroidism, identified in patients spanning the globe [2]. Diagnosis and appropriate treatments are critical for the prognosis of patients with GD. A. Sun et al Biol Res (2020) 53:32 recent observational study in Italy reported that the clinical phenotype of GD is becoming milder, likely due to increased awareness on thyroid disease and the availability of sensitive diagnostic tests, in conjunction with timely and effective treatments [3]. The importance of improving the understanding of the molecular and intermolecular interactions and the key signaling pathways affected by Graves’ disease persists
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