Department of Clinical Laboratory, The Third Hospital of Jilin University, No. 126, Xiantai Street, Changchun, 130033, Jilin, China.
Department of Clinical Laboratory, The First Hospital of Jilin University, No. 1, Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, China.
BMC Med Genomics. 2021 May 18;14(1):133. doi: 10.1186/s12920-021-00931-0.
Our study aimed to investigate signature RNAs and their potential roles in type 1 diabetes mellitus (T1DM) using a competing endogenous RNA regulatory network analysis.
Expression profiles of GSE55100, deposited from peripheral blood mononuclear cells of 12 T1DM patients and 10 normal controls, were downloaded from the Gene Expression Omnibus to uncover differentially expressed long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs). The ceRNA regulatory network was constructed, then functional and pathway enrichment analysis was conducted. AT1DM-related ceRNA regulatory network was established based on the Human microRNA Disease Database to carry out pathway enrichment analysis. Meanwhile, the T1DM-related pathways were retrieved from the Comparative Toxicogenomics Database (CTD).
In total, 847 mRNAs, 41 lncRNAs, and 38 miRNAs were significantly differentially expressed. The ceRNA regulatory network consisted of 12 lncRNAs, 10 miRNAs, and 24 mRNAs. Two miRNAs (hsa-miR-181a and hsa-miR-1275) were screened as T1DM-related miRNAs to build the T1DM-related ceRNA regulatory network, in which genes were considerably enriched in seven pathways. Moreover, three overlapping pathways, including the phosphatidylinositol signaling system (involving PIP4K2A, INPP4A, PIP4K2C, and CALM1); dopaminergic synapse (involving CALM1 and PPP2R5C); and the insulin signaling pathway (involving CBLB and CALM1) were revealed by comparing with T1DM-related pathways in the CTD, which involved four lncRNAs (LINC01278, TRG-AS1, MIAT, and GAS5-AS1).
The identified signature RNAs may serve as important regulators in the pathogenesis of T1DM.
本研究旨在通过竞争性内源 RNA 调控网络分析，研究 1 型糖尿病（T1DM）相关特征 RNA 及其潜在作用。
从基因表达综合数据库中下载 GSE55100 数据集，该数据集包含 12 例 T1DM 患者和 10 例正常对照者外周血单个核细胞的表达谱，以揭示差异表达的长非编码 RNA（lncRNA）、mRNA 和 microRNA（miRNA）。构建 ceRNA 调控网络，然后进行功能和通路富集分析。基于人类 microRNA 疾病数据库构建 AT1DM 相关 ceRNA 调控网络，进行通路富集分析。同时，从比较毒理学基因组数据库（CTD）中检索与 T1DM 相关的通路。
共筛选出 847 个 mRNA、41 个 lncRNA 和 38 个 miRNA 表达显著差异。ceRNA 调控网络包含 12 个 lncRNA、10 个 miRNA 和 24 个 mRNA。筛选出 2 个 miRNA（hsa-miR-181a 和 hsa-miR-1275）作为 T1DM 相关 miRNA 构建 T1DM 相关 ceRNA 调控网络，其中基因在 7 个通路中显著富集。此外，通过与 CTD 中与 T1DM 相关的通路比较，发现了三个重叠通路，包括磷酸肌醇信号系统（涉及 PIP4K2A、INPP4A、PIP4K2C 和 CALM1）、多巴胺能突触（涉及 CALM1 和 PPP2R5C）和胰岛素信号通路（涉及 CBLB 和 CALM1），涉及 4 个 lncRNA（LINC01278、TRG-AS1、MIAT 和 GAS5-AS1）。
所鉴定的特征 RNA 可能作为 T1DM 发病机制中的重要调节剂。
