Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, The Second Xiangya Hospital of Central South University, Changsha, China.
Diabetes Metab Res Rev. 2024 Nov;40(8):e70006. doi: 10.1002/dmrr.70006.
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.
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.
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.
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.
环状 RNA（circRNA）与暴发性 1 型糖尿病（FT1D）和 1 型糖尿病（T1D）有关。然而，FT1D 和 T1D 之间的 circRNA 差异仍不清楚。我们的目的是鉴定 FT1D 和 T1D 患者外周血单个核细胞（PBMC）衍生的 circRNA，并探讨其潜在功能。
从 6 例 FT1D 患者和年龄、性别和病程匹配的 T1D 患者中提取 PBMC。利用 Arraystar 人类 circRNA 芯片获得 circRNA 表达谱。选择 7 个异常表达的 circRNA 进行实时定量 PCR（RT-qPCR）在另一个独立队列（FT1D 组 n=35，T1D 组 n=70，对照组 n=100）中确定表达水平。通过生物信息学分析预测 circRNA 的生物学功能、circRNA-miRNA-mRNA 网络和编码潜力。
总共在 FT1D 和 T1D 中鉴定出 145 个差异表达的 circRNA，其中 63 个上调和 82 个下调 circRNA。在选择确定表达水平的 7 个异常表达的 circRNA 中，hsa_circRNA_038288、hsa_circRNA_104405 和 hsa_circRNA_405498 得到成功验证。生物信息学分析表明，circRNA 亲本基因的大多数都富集在 RNA 转运、泛素介导的蛋白水解和焦点粘连等信号通路中。Hsa_circRNA_038288 似乎在 51 个与免疫调节和糖尿病相关的 circRNA-miRNA-mRNA 信号通路中发挥作用。此外，hsa_circRNA_038288 可能具有编码潜力，并且参与了 FT1D 和 T1D 的进展。
FT1D 和 T1D 患者免疫细胞来源的 circRNA 存在显著差异，为区分 FT1D 和 T1D 的分子机制提供了新的见解。
