Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China.
Front Immunol. 2020 Sep 29;11:576903. doi: 10.3389/fimmu.2020.576903. eCollection 2020.
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 () gene in patients with T1DM, termed as . Subsequent assays revealed that 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 (), 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.
环形 RNA(circRNAs)是一类由 5'和 3'端反向剪接形成的共价闭合的非编码 RNA 分子。生物信息学和大规模测序的快速发展,已经鉴定出了具有功能的 circRNAs。尽管总体呈上升趋势,但针对 circRNAs 在免疫性疾病中作用的研究仍然相对较少。在本研究中,我们通过对 1 型糖尿病(T1DM)患儿外周血单个核细胞(PBMCs)的微阵列分析,获得了一个差异表达的 circRNA 表达谱。我们在 T1DM 患者中鉴定了一个由 MYB 原癌基因样 2()基因反向剪接的差异表达的 circRNA,命名为 。随后的实验表明, 可以作为 miR-199a-5p 的海绵,释放其靶基因,由酪氨酸蛋白磷酸酶非受体型 11 基因()编码的 Src 同源 2(SH2)含蛋白酪氨酸磷酸酶 2(SHP2),并进一步抑制由 I 型干扰素(IFN-I)触发的 JAK-STAT 信号通路,抑制巨噬细胞介导的炎症,这表明 circRNAs 在 T1DM 中具有重要作用,是治疗 T1DM 的一种有前途的治疗分子。