Hsa_circ_0060450 Negatively Regulates Type I Interferon-Induced Inflammation by Serving as miR-199a-5p Sponge in Type 1 Diabetes Mellitus

Abstract

Circular RNAs (circRNAs) constitute a class of covalently circular non-coding RNA molecules formed by 5′ and 3′ end back-splicing. The rapid development of bioinformatics and large-scale sequencing has led to the identification of functional circRNAs. Despite an overall upward trend, studies focusing on the roles of circRNAs in immune diseases remain relatively scarce. In the present study, we obtained a differential circRNA expression profile based on microarray analysis of peripheral blood mononuclear cells (PBMCs) in children with type 1 diabetes mellitus (T1DM). We characterized one differentially expressed circRNA back-spliced from the MYB Proto-Oncogene Like 2 ( MYBL2 ) gene in patients with T1DM, termed as hsa_circ_0060450 . Subsequent assays revealed that hsa_circ_0060450 can serve as the sponge of miR-199a-5p, release its target gene, Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), encoded by the tyrosine-protein phosphatase non-receptor type 11 gene ( PTPN11 ), and further suppress the JAK-STAT signaling pathway triggered by type I interferon (IFN-I) to inhibit macrophage-mediated inflammation, which indicates the important roles of circRNAs in T1DM and represents a promising therapeutic molecule in the treatment of T1DM.

Revealing New Landscape of Turbot (Scophthalmus maximus) Spleen Infected with Aeromonas salmonicida through Immune Related circRNA-miRNA-mRNA Axis

“…circRNAs showed significant regulation in Type 1 Diabetes Mellitus. Hsa_circ_0060450 could release the target gene (SHP2 and PTPN11) of miR-199a-5p and further suppressed the JAK-STAT signaling pathway triggered by type I interferon (IFN-I) to inhibit macrophage-mediated inflammation [55]. In a word, circRNA-miRNA-mRNA regulatory networks existed and played a pivotal role in a variety of physiological and pathological processes.…”

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

“…One is the circRNA, lncRNA, and mRNA expression profile GSE133225, and the other one is the miRNA expression profile GSE133217. Both expression profiles were provided by Zhang Caiyan and Zhou Yufeng, 25 , 36 and included 4 peripheral blood mononuclear cells (PBMCs) samples from T1DM patients and 4 PBMCs samples from healthy volunteers.…”

“…Human THP-1 cell line from Procell Life Science&Technology Co., Ltd. (Wuhan, China) was cultured in the RPMI-1640 medium supplied with 10% fetal bovine serum (FBS, Gibco, Gaithersburg, MD, USA) and 1% penicillin-streptomycin (Gibco) at 37°C with 5% CO 2 . Then, according to a previous study, 36 THP-1-derived macrophages were induced by treating with 50 ng/mL phorbol 12-myristate 13-acetate (PMA) for 48 h. Cell transfection was performed using Lipofectamine 3000 reagent (Invitrogen, USA) with the chemically synthesized circRNA small interfering RNAs (si-circ, sequence: 5ʹ-AGTACAACAATTCAGGTGATT-3ʹ), and small interfering RNAs negative control (si-NC, sequence: 5ʹ-UUCUCCGAACGUGUCACGUTT-3ʹ). After 48 h of transfection, the macrophages were treated with type I interferon (IFN-I, 1000 units/mL, PBL Assay Science, USA) to induce the inflammation.…”

Circular RNAs as Novel Regulators of β-Cell Functions under Physiological and Pathological Conditions

“…The level of circRNAs varies in different tissues and according to cellular conditions [ 7 , 80 ]. Moreover, as outlined in the previous chapters, the expression of some circRNAs is altered under disease states [ 7 , 8 , 9 , 10 , 11 ], including diabetes [ 72 , 73 , 81 ]. Finally, some circRNAs are secreted in the extracellular space and are abundant in body fluids (blood, saliva, urine, cerebrospinal fluid) and are detectable in liquid biopsies [ 82 , 83 ].…”