Department of Endocrinology and Metabolism, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
BMC Endocr Disord. 2022 May 9;22(1):119. doi: 10.1186/s12902-022-01038-y.
Type 1 diabetes (T1D) is a T lymphocyte-mediated and B lymphocyte-assisted autoimmune disease. We aimed to identify abnormally expressed genes in peripheral blood mononuclear cells (PBMCs) of T1D and explore their possible molecular regulatory network.
Expression datasets were downloaded from the Gene Expression Omnibus (GEO) database. Then, the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) were identified, and functional enrichment and immune cell infiltration analysis were performed. The starBase, miRTarBase, TarBase, JASPAR, ENCODE, and TRRUST databases constructed the miRNA-mRNA-TF regulatory network. The ROC curves were plotted to evaluate the sensitivity and specificity of miRNAs and mRNAs.
A total of 216 DEGs directly or indirectly related to type I diabetes mellitus, natural killer cell-mediated cytotoxicity, Th1, and Th2 cell differentiation, and the IL-17 and TNF signaling pathways were obtained. The miRNA-mRNA-TF network indicates that miR-320a and SOX5 are the only miRNAs and TFs that both target ADM and RRAGD. The ROC curves showed that ADM (0.9375), RRAGD (0.8958), and hsa-mir-320a (0.9417) had high accuracy in T1D diagnosis.
The constructed regulatory networks, including miR-320a/ADM/SOX5 and miR-320a/RRAGD/SOX5, may provide new insight into the mechanisms of development and progression in T1D.
1 型糖尿病（T1D）是一种 T 淋巴细胞介导、B 淋巴细胞辅助的自身免疫性疾病。我们旨在鉴定 T1D 患者外周血单个核细胞（PBMC）中异常表达的基因，并探讨其可能的分子调控网络。
从基因表达综合数据库（GEO）下载表达数据集。然后，鉴定差异表达基因（DEGs）和差异表达 microRNA（DEmiRNAs），并进行功能富集和免疫细胞浸润分析。利用 starBase、miRTarBase、TarBase、JASPAR、ENCODE 和 TRRUST 数据库构建 microRNA-mRNA-TF 调控网络。绘制 ROC 曲线评估 microRNAs 和 mRNAs 的灵敏度和特异性。
获得了 216 个直接或间接与 1 型糖尿病、自然杀伤细胞介导的细胞毒性、Th1 和 Th2 细胞分化以及 IL-17 和 TNF 信号通路相关的差异表达基因。miRNA-mRNA-TF 网络表明，miR-320a 和 SOX5 是唯一同时靶向 ADM 和 RRAGD 的 microRNA 和 TF。ROC 曲线显示 ADM（0.9375）、RRAGD（0.8958）和 hsa-mir-320a（0.9417）在 T1D 诊断中具有较高的准确性。
构建的调控网络，包括 miR-320a/ADM/SOX5 和 miR-320a/RRAGD/SOX5，可能为 T1D 的发病机制和进展提供新的见解。
