Understanding Competitive Endogenous RNA Network Mechanism in Type 1 Diabetes Mellitus Using Computational and Bioinformatics Approaches

Abstract

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.

Keywords:

• type 1 diabetes mellitus
• ceRNA network
• peripheral blood mononuclear cell
• macrophage

Abbreviations

BP, biological processes; CAP, c-Cbl-associated protein; CC, cellular components; circRNA, circular RNA; ceRNA, competitive endogenous RNA; DEcircRNAs, differentially expressed circRNAs; DElncRNAs, differentially expressed lncRNAs; DEGs, differentially expressed genes; DEmRNAs, differentially expressed mRNAs; ECM, extracellular matrix components; GEO, Gene Expression Omnibus; GO, Gene Ontology; IFN-I, type I interferon; KEGG, Kyoto Encyclopedia of Genes and Genomes; lncRNA, long non-coding RNA; miRNA, microRNA; MRE, miRNA response element; MF, molecular functions; ncRNA, non-coding RNA; PBMCs, peripheral blood mononuclear cells; PMA, phorbol 12-myristate 13-acetate; qRT-PCR, Quantitative real-time PCR; T1DM, Type 1 diabetes mellitus.

Author Contributions

Both authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflicts of interest for this work.

Additional information

Funding

There is no funding to report.