Differences in Immune Cell-Derived Circular RNA Between Fulminant Type 1 Diabetes and Type 1 Diabetes

Aims: Circular RNAs (circRNAs) are associated with fulminant type 1 diabetes (FT1D) and type 1 diabetes (T1D). However, the differences in circRNAs between FT1D and T1D remain unclear. Our objective is to identify peripheral blood mononuclear cells (PBMCs)-derived circRNAs in FT1D and T1D and explore their potential functions.

Materials and methods: PBMCs were extracted from six patients with FT1D and age-, sex-, and duration-matched T1D patients. The Arraystar Human circRNA Array was utilised to obtain circRNA expression profiles. Seven aberrantly expressed circRNAs were selected for determining expression levels in another independent cohort (FT1D subjects n = 35, T1D subjects n = 70, and controls n = 100) using real-time quantitative PCR (RT-qPCR). Biological functions, circRNA-miRNA-mRNA networks, and the coding potential of circRNAs were predicted through bioinformatics analysis.

Results: In total, 145 differentially expressed circRNAs were identified in FT1D and T1D, with 63 upregulated and 82 downregulated circRNAs. Hsa_circRNA_038288, hsa_circRNA_104405, and hsa_circRNA_405498 were successfully validated among the 7 aberrantly expressed circRNAs selected to determine expression levels. Bioinformatics analysis revealed that majority of the parent genes of circRNAs are enriched in signalling pathways such as RNA transport, ubiquitin-mediated proteolysis, and focal adhesion. Hsa_circRNA_038288 appears to play a role in 51 circRNA-miRNA-mRNA signalling pathways associated with immune regulation and diabetes. Additionally, hsa_circRNA_038288 potentially exhibits coding potential and is involved in the progression of both FT1D and T1D.

Conclusions: Significant differences in immune cell-derived circRNAs were found between FT1D and T1D patients, offering novel insights into the molecular mechanisms that distinguish FT1D from T1D.