Microarray profiling and functional analysis of differentially expressed plasma exosomal circular RNAs in Graves' disease
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Published on: January 22, 2014
Ying Sun1, Wei Wang1, Yuxiao Tang1
1Department of Endocrinology, Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, Shandong, China.
Background:
Circulating 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.
Methods:
Serum 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.
Results:
There 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.
Conclusions:
hsa_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.
Insights
Graves' disease (GD) involves altered exosomal circular RNAs (circRNAs). Researchers identified hsa_circRNA_000102 as elevated in GD patients, suggesting roles in immune activation pathways like viral infection.
Area of Science:
- Endocrinology
- Molecular Biology
- Immunology
Background:
- Circulating RNAs (circRNAs) play roles in cellular functions.
- Exosomal circRNAs offer insights into Graves' disease (GD) pathogenesis and treatment.
- Understanding circRNA profiles in GD can reveal disease mechanisms.
Purpose of the Study:
- To profile differentially expressed circRNAs (DEcRs) in plasma exosomes of GD patients.
- To investigate the functions of identified DEcRs using bioinformatics analyses.
- To explore potential therapeutic targets for Graves' disease.
Main Methods:
- Exosomes were isolated from GD patients and healthy controls using ultracentrifugation.
- circRNA microarrays were used for profiling, followed by RT-qPCR validation.
- circRNA/microRNA/mRNA networks and pathway analyses (GO, KEGG) were performed.
Main Results:
- Fifteen DEcRs were identified in GD patients.
- hsa_circRNA_000102 was confirmed as significantly up-regulated in plasma exosomes of GD patients.
- Functional analysis predicted involvement in immune activation pathways, including viral infection and interferon-beta signaling.
Conclusions:
- hsa_circRNA_000102 is a key up-regulated exosomal circRNA in Graves' disease.
- This circRNA and its associated genes are implicated in immune system activation pathways.
- The findings highlight potential mechanisms of immune dysregulation in GD.
