Circulating circular RNAs profiles associated with type 1 diabetes

Abstract

Aims: Circular RNAs (circRNAs) have recently been shown to exert important effects in human diseases. However, the roles of circRNAs in type 1 diabetes (T1D) are largely unknown. This study is to identify the circRNA expression profiles in the peripheral blood of patients with T1D and predict their potential regulatory mechanisms and coding potential.

Methods: CircRNA expression profiles were detected by Arraystar human circRNA microarray. With real-time PCR validation, multiple bioinformatics approaches were used to explore their biological functions, construct the circRNA-miRNA-mRNA interactions, and predict circRNA coding potential.

Results: A total of 93 differentially expressed circular transcripts were identified in T1D compared with controls, among which 30 were upregulated, and 63 were downregulated. Two circRNAs were identified to have significant differences by RT-PCR. Gene ontology analysis enriched terms such as cellular protein metabolic process, cytoplasm and zinc ion binding. The proposed molecular functions of these differentially expressed circRNAs, including cellular protein metabolic process, cytoplasm, and binding, may contribute to T1D. The most enriched pathways for these circRNAs were involved in protein processing in the endoplasmic reticulum. Hsa_circ_0072697 may be involved in 50 circRNA-miRNA-mRNA signalling pathways related to diabetes, such as circ_0072697-miR-15a-UBASH3A network. Furthermore, hsa_circ_0071224, hsa_circ_0002437, hsa_circ_0084429, hsa_circ_0072697, and hsa_circ_0000787 in T1D were considered to have the most coding potential involved in the pathogenesis of T1D.

Conclusions: These results showed that circRNAs are aberrantly expressed in the peripheral blood of patients with T1D and may play potential actions by interactions with miRNA and circRNA-derived peptides in the development of T1D.

Keywords: ceRNAs; circRNAs; circular RNAs; non-coding RNA; type 1 diabetes.