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.

Circular RNAs in diabetes and its complications: Current knowledge and future prospects

“…Additionally, 1922 markedly expression circRNAs were found in mouse islet β-cells induced by various cytokines, such as interleukin-1β (IL-1β), interferon-γ(INF-γ), and tumor necrosis factor-α (TNF-α) ( Wang et al, 2021a ). In order to clarify the role of circRNA in T1D, Yi et al ( Yi and Cheng, 2021 ) established the circRNA-lncRNA-miRNA-mRNA ceRNA regulatory network for T1D using computational and bioinformatic approaches. However, studies on therapeutic circRNAs in T1D are limited, it needs to be proven by a large amount of data in the future.…”

Expression of lncRNA LINC00943 in lung squamous cell carcinoma and its relationship with tumor progression

“…It has been reported that miRNAs, as conserved non-coding single-stranded RNA molecules, are involved in a variety of physiological and pathological processes [ 24 ]. As a sponge of miRNAs, lncRNA forms the corresponding lncRNA/miRNA axis to regulate transcription and tumor cell proliferation [ 25 , 26 ]. This study predicted that LINC00943 and miR-196b-5p have binding sites.…”

Potential of ATP5MG to Treat Metabolic Syndrome-Associated Cardiovascular Diseases

“…Key ceRNA pairs in metabolic pathways may participate in right ventricular dysfunction (52). circRNA/lncRNA/miRNA/mRNA inhibits macrophage inflammation in type 1 diabetes mellitus (T1DM) (53). AC063977.6/miR-338-3p/PFKFB2 may regulate metabolic event during Intervertebral disc degeneration (IDD) pathogenesis (54).…”