National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan, China.
J Immunol Res. 2022 Oct 27;2022:3625052. doi: 10.1155/2022/3625052. eCollection 2022.
Both exosome and circular RNA (circRNA) have been reported to participate in the pathogenesis of type 1 diabetes mellitus (T1DM). However, the exact role of exosomal circRNA in T1DM is largely unknown. Here, we identified the exosomal circRNA expression profiles in the plasma of T1DM patients and explored their potential function using bioinformatics analysis. . Exosomes were extracted by the size exclusion chromatography method from plasma of 10 T1DM patients and 10 age- and sex- matched control subjects. Illumina Novaseq6000 platform was used to detect the exosomal circRNA expression profiles. Multiple bioinformatics analysis was applied to investigate the potential biological functions of exosomal circRNAs.
A total of 784 differentially expressed exosomal circRNAs have been identified in T1DM patients, of which 528 were upregulated and 256 were downregulated. Gene Ontology analysis enriched terms such as protein ubiquitination involved in ubiquitin-dependent protein catabolic protein (GO:0042787), membrane (GO:0016020), and GTPase activator activity (GO:0005096). The most enriched pathway in Kyoto Encyclopedia of Genes and Genomes was ubiquitin-mediated proteolysis (ko04120). The miRNA-targeting prediction method was used to identify the miRNAs that bind to circRNAs, and circRNA-miRNA-mRNA pathways were constructed, indicating that interactions between circRNA, miRNA, and gene might be involved in the disease progression.
The present study identified the exosomal circRNA expression profiles in T1DM for the first time. Our results threw novel insights into the molecular mechanisms of T1DM.
外泌体和环状 RNA(circRNA)都被报道参与 1 型糖尿病(T1DM)的发病机制。然而,外泌体 circRNA 在 T1DM 中的确切作用在很大程度上尚不清楚。在这里,我们鉴定了 T1DM 患者血浆中外泌体 circRNA 的表达谱,并通过生物信息学分析探索了它们的潜在功能。从 10 名 T1DM 患者和 10 名年龄和性别匹配的对照者的血浆中通过尺寸排阻层析法提取外泌体。使用 Illumina Novaseq6000 平台检测外泌体 circRNA 的表达谱。应用多种生物信息学分析方法研究外泌体 circRNA 的潜在生物学功能。
在 T1DM 患者中总共鉴定出 784 个差异表达的外泌体 circRNA,其中 528 个上调,256 个下调。基因本体论分析富集了与泛素依赖性蛋白水解有关的蛋白泛素化等术语(GO:0042787)、膜(GO:0016020)和 GTP 酶激活活性(GO:0005096)。京都基因与基因组百科全书最丰富的途径是泛素介导的蛋白水解(ko04120)。使用 miRNA 靶向预测方法鉴定与 circRNA 结合的 miRNA,并构建 circRNA-miRNA-mRNA 通路,表明 circRNA、miRNA 和基因之间的相互作用可能参与疾病进展。
本研究首次鉴定了 T1DM 中外泌体 circRNA 的表达谱。我们的结果为 T1DM 的分子机制提供了新的见解。