Abstract
Aims/Hypothesis: Circular RNAs (circRNAs), a class of endogenous RNAs, have emerged as an enigmatic class of RNAs. Little is known about their value in diagnosis of type 1 diabetes. We aimed to explore circRNA profiles for risk T1D in both mouse and human serum, and studied the interplay between microRNA and circular RNAs in human serum. Methods: We examined circRNA expression profiles during T1D development in nine NOD mice using Arraystar circRNA microarray. Human serum samples from 107 new onset T1D patients and 40 healthy control (HC) were used to profile miRNA expression. Furthermore, 50 T1D and 50 HC were randomly selected from this cohort for circRNA profiling using circRNA microarray. Results: 134 circRNAs in NOD mice were significantly different in T1D mice compared to normal control or insulitis (FDR<0.10029. In human serum, we identified 50 circRNAs differentially expressed between T1D and HC. By comparing circRNAs in NOD mouse model that might be homologous to human circRNA, two of the circRNAs showed suggestive evidence for differential expression between normal control, insulitis and T1D (FDR<0.2). Furthermore, 87 human serum miRNAs were significantly regulated in T1D compared to HC, 23 among those were highly negatively associated with the 50 differentially expressed circRNAs. Conclusions: We have identified a serum circRNA and miRNA pattern of T1D, and they may be a potential novel and stable biomarker for the diagnosis of T1D. Disclosure C. Yin: None. Q. Mi: None. Funding National Institute of Allergy and Infectious Diseases (R01AI119041, R01AI108612)
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