Diabetes, Metabolic Syndrome and Obesity (Sep 2021)
Understanding Competitive Endogenous RNA Network Mechanism in Type 1 Diabetes Mellitus Using Computational and Bioinformatics Approaches
Abstract
Xuanzi Yi,1,* Xu Cheng2,3,* 1Department of Medicine II, Division of Endocrinology and Diabetology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, 79106, Germany; 2Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, 79106, Germany*These authors contributed equally to this workCorrespondence: Xuanzi YiDepartment of Medicine II, Division of Endocrinology and Diabetology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, Freiburg, 79106, GermanyTel/Fax +49 761 270-73270Email [email protected]: 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.Keywords: type 1 diabetes mellitus, ceRNA network, peripheral blood mononuclear cell, macrophage
