Type 1 Diabetes Mellitus-Related circRNAs Regulate CD4+ T Cell Functions

Circular RNAs (circRNAs) participate in development of malignancies through its active role as a "miRNA sponge." Their roles in type 1 diabetes mellitus (T1DM) pathogenesis are elusive. Here, the important role of circRNAs in T1DM was explored. circRNA profiling was performed for isolated CD4+ T cells from blood of T1DM and healthy volunteers. There were 257 differentially expressed circRNAs. Only three upregulated DEcircRNAs (hsa_circ_0000324, hsa_circ_0001853, and hsa_circ_0068797) were consistent with the GEO database. Through KEGG analyses, it was found that the three DEcircRNAs were associated with 11 miRNAs and 8 immune-related target genes (mRNA). Further analysis found that four miRNAs, two circRNAs, and four mRNAs were associated with nine circRNA-miRNA-mRNA networks. This confirmed the requirements of sponge mechanisms. The qRT-PCR analysis revealed that circRNA000324/miRNA675-5p/MAPK14 and circRNA000324/miRNA-675-5p/SYK may be potential mechanisms in regulation of differentiation and proliferation of CD4+ T cell in patients with T1DM. Therefore, targeting circRNA to regulate cellular immune responses by regulating CD4+ T cell differentiation may be a new strategy for the treatment of T1DM.