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, China.
Front Endocrinol (Lausanne). 2022 May 12;13:822221. doi: 10.3389/fendo.2022.822221. eCollection 2022.
Exosomes contain several types of transcripts, including long non-coding RNAs (lncRNAs), and have been shown to exert important effects in human diseases. However, the roles of exosomal lncRNAs in type 1 diabetes mellitus (T1DM) have not been well investigated. In the present study, we characterized the plasma-derived exosomal lncRNAs expression profiles of T1DM and predict their potential function in the pathogenesis of T1DM.
Exosomal lncRNA expression profiles were detected by Illumina Hiseq platform (T1DM subjects N=10; age-, sex- matched Control subjects N=10). Six exosomal lncRNAs were selected to validate their expression level by using quantitative real-time PCR (qRT-PCR) (T1DM subjects N=30; age-, sex- matched Control subjects N=30). Bioinformatics analysis approaches were carried out to explore the potential biological function of differentially expressed lncRNAs.
A total of 162 differentially expressed exosomal lncRNAs were identified in T1DM patients compared with control subjects, among which 77 up-regulated and 85 down-regulated. The expression level of the selected six lncRNAs didn't show significant difference in the following qRT-PCR analysis. Gene Ontology analysis enriched terms such as activation of phospholipase D activity, neuronal cell body membrane, and calcium sensitive guanylate cyclase activator activity for cis-acting genes of lncRNAs, and metal ion binding for trans-acting genes. The most enriched Kyoto Encyclopedia of Genes and Genomes pathways for the lncRNAs were associated with oxidative phosphorylation and Parkinson's disease for cis-acting genes, and pathways in cancer as well as focal adhesion for trans-acting genes.
This study characterized the lncRNA profiles of plasma-derived exosomes from T1DM for the first time and these results highlighted the potential role of exosomal lncRNAs in T1DM pathogenesis. A better understanding of exosomal lncRNA profiling will provide novel insights into its molecular mechanisms.
外泌体包含多种类型的转录本,包括长非编码 RNA(lncRNA),并已被证明在外泌体 lncRNA 在 1 型糖尿病(T1DM)中的作用。然而,外泌体 lncRNA 在 1 型糖尿病中的作用尚未得到充分研究。在本研究中,我们描述了 T1DM 患者血浆来源的外泌体 lncRNA 表达谱,并预测了它们在 T1DM 发病机制中的潜在功能。
采用 Illumina Hiseq 平台检测外泌体 lncRNA 表达谱(T1DM 组 N=10;年龄、性别匹配的对照组 N=10)。选择 6 个外泌体 lncRNA 用实时荧光定量 PCR(qRT-PCR)验证其表达水平(T1DM 组 N=30;年龄、性别匹配的对照组 N=30)。采用生物信息学分析方法探讨差异表达 lncRNA 的潜在生物学功能。
与对照组相比,T1DM 患者中共有 162 个差异表达的外泌体 lncRNA,其中上调 77 个,下调 85 个。在随后的 qRT-PCR 分析中,所选 6 个 lncRNA 的表达水平没有明显差异。基因本体论分析富集了 lncRNA 顺式作用基因的磷酸酶 D 活性激活、神经元细胞体膜和钙敏鸟苷酸环化酶激活剂活性等术语,以及反式作用基因的金属离子结合等术语。顺式作用基因中最富集的京都基因与基因组百科全书通路与氧化磷酸化和帕金森病有关,反式作用基因中与癌症通路和焦点粘附有关。
本研究首次描述了 T1DM 患者血浆衍生外泌体的 lncRNA 谱,这些结果突出了外泌体 lncRNA 在 T1DM 发病机制中的潜在作用。更好地了解外泌体 lncRNA 谱将为其分子机制提供新的见解。