Abstract
Circular RNAs (circRNAs) constitute a class of covalently circular non-coding RNA molecules formed by 5′ and 3′ end back-splicing. The rapid development of bioinformatics and large-scale sequencing has led to the identification of functional circRNAs. Despite an overall upward trend, studies focusing on the roles of circRNAs in immune diseases remain relatively scarce. In the present study, we obtained a differential circRNA expression profile based on microarray analysis of peripheral blood mononuclear cells (PBMCs) in children with type 1 diabetes mellitus (T1DM). We characterized one differentially expressed circRNA back-spliced from the MYB Proto-Oncogene Like 2 (MYBL2) gene in patients with T1DM, termed as hsa_circ_0060450. Subsequent assays revealed that hsa_circ_0060450 can serve as the sponge of miR-199a-5p, release its target gene, Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), encoded by the tyrosine-protein phosphatase non-receptor type 11 gene (PTPN11), and further suppress the JAK-STAT signaling pathway triggered by type I interferon (IFN-I) to inhibit macrophage-mediated inflammation, which indicates the important roles of circRNAs in T1DM and represents a promising therapeutic molecule in the treatment of T1DM.
Highlights
Type 1 diabetes (T1DM) is an autoimmune disease, known as insulin-dependent diabetes mellitus, owing to the complete absence of insulin secretion
We obtained a differential circRNA expression profile based on microarray analysis of peripheral blood mononuclear cells (PBMCs) in children with type 1 diabetes mellitus (T1DM)
We verified the expressions of the top 10 circRNAs (Figure 1B) with the highest differential expression fold in a larger population of clinical samples of PBMCs collected from 20 T1DM children and 20 healthy controls by Reverse Transcription Quantitative PCR (RT-qPCR), and the results showed hsa_circ_0060450 was detectable and significantly upregulated in PBMCs of T1DM patients than controls (Figure 1C)
Summary
Type 1 diabetes (T1DM) is an autoimmune disease, known as insulin-dependent diabetes mellitus, owing to the complete absence of insulin secretion. During the pathogenesis of T1DM, insulin-producing pancreatic β cells are attacked by the immune system, resulting in destruction of islet function and decreased insulin secretion [1, 2]. In addition to adaptive immune cells, innate immune cells are involved in the onset of T1DM [6,7,8]. Emerging evidence suggests that the absence of Toll-like receptor signaling in innate immune cells, caused by TIR-domain-containing adapter-inducing interferonβ (TRIF) deficiency, has a protective effect against diabetes in the non-obese diabetic (NOD) mouse via alteration of the gut microbiota and reduced immune cell activation [9]
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