Background: Type 1 diabetes mellitus (T1DM), an autoimmune disease with a genetic tendency, has an increasing prevalence. Long non-coding RNA (lncRNA) and circular RNA (circRNA) are receiving increasing attention in disease pathogenesis. However, their roles in T1DM are poorly understood. The present study aimed at identifying signature lncRNAs and circRNAs and investigating their roles in T1DM using the competing endogenous RNA (ceRNA) network analysis.
Methods: The T1DM expression profile was downloaded from Gene Expression Omnibus (GEO) database to identify the differentially expressed circRNAs, lncRNAs, and mRNAs. The biological functions of these differentially expressed circRNAs, lncRNAs, and mRNAs were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Targeting relationships of circRNA-miRNA, lncRNA-miRNA, and miRNA-mRNA were predicted, and the circRNA-lncRNA-miRNA-mRNA ceRNA regulatory network was established. Finally, qRT-PCR was applied to identify the effect of hsa_circ_0002202 inhibition on the IFN-I induced macrophage inflammation.
Results: A total of 178 circRNAs, 404 lncRNAs, and 73 mRNAs were identified to be abnormally expressed in T1DM samples. Functional enrichment analysis results indicated that the differentially expressed genes were mainly enriched in extracellular matrix components and macrophage activation. CeRNA regulatory network showed that circRNAs and lncRNAs regulate mRNAs through integrate multiple miRNAs. In addition, in vitro experiments showed that hsa_circ_0002202 inhibition suppressed the type I interferon (IFN-I)-induced macrophage inflammation.
Conclusion: In the present study, the circRNA-lncRNA-miRNA-mRNA ceRNA regulatory network in T1DM was established for the first time. We also found that hsa_circ_0002202 inhibition suppressed the IFN-I-induced macrophage inflammation. Our study may lay a foundation for future studies on the ceRNA regulatory network in T1DM.



中文翻译：

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使用计算和生物信息学方法了解 1 型糖尿病的竞争性内源性 RNA 网络机制

背景： 1 型糖尿病（T1DM）是一种具有遗传倾向的自身免疫性疾病，其患病率越来越高。长链非编码 RNA (lncRNA) 和环状 RNA (circRNA) 在疾病发病机制中越来越受到关注。然而，人们对它们在 T1DM 中的作用知之甚少。本研究旨在识别特征性 lncRNA 和 circRNA，并使用竞争性内源性 RNA (ceRNA) 网络分析研究它们在 T1DM 中的作用。
方法：T1DM 表达谱从 Gene Expression Omnibus (GEO) 数据库下载，以识别差异表达的 circRNA、lncRNA 和 mRNA。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析分析了这些差异表达的circRNA、lncRNA和mRNA的生物学功能。预测了circRNA-miRNA、lncRNA-miRNA和miRNA-mRNA的靶向关系，建立了circRNA-lncRNA-miRNA-mRNA ceRNA调控网络。最后，应用 qRT-PCR 来确定 hsa_circ_0002202 抑制对 IFN-I 诱导的巨噬细胞炎症的影响。
结果：在 T1DM 样本中，共有 178 个 circRNA、404 个 lncRNA 和 73 个 mRNA 被鉴定为异常表达。功能富集分析结果表明，差异表达基因主要富集于细胞外基质成分和巨噬细胞活化。CeRNA 调控网络表明，circRNA 和 lncRNA 通过整合多个 miRNA 来调控 mRNA。此外，体外实验表明，hsa_circ_0002202 抑制抑制了 I 型干扰素 (IFN-I) 诱导的巨噬细胞炎症。
结论：本研究首次建立了T1DM中的circRNA-lncRNA-miRNA-mRNA ceRNA调控网络。我们还发现 hsa_circ_0002202 抑制抑制了 IFN-I 诱导的巨噬细胞炎症。我们的研究可能为未来 T1DM 中 ceRNA 调控网络的研究奠定基础。