暴发性 1 型糖尿病与 1 型糖尿病免疫细胞衍生环状 RNA 的差异。

IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes/Metabolism Research and Reviews Pub Date : 2024-11-04 DOI:10.1002/dmrr.70006
Wenfeng Yin, Shuoming Luo, Junlin Qiu, Zilin Xiao, Ziwei Zhang, Rui Wang, Zhiguo Xie, Xia Li, Zhiguang Zhou
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引用次数: 0

摘要

目的:循环RNA(circRNAs)与暴发性1型糖尿病(FT1D)和1型糖尿病(T1D)有关。 然而,FT1D和T1D之间循环RNAs的差异仍不清楚。我们的目的是鉴定 FT1D 和 T1D 中外周血单核细胞(PBMCs)产生的 circRNAs,并探索它们的潜在功能:从 6 名 FT1D 患者以及年龄、性别和病程匹配的 T1D 患者身上提取外周血单核细胞。利用 Arraystar 人类 circRNA 阵列获得 circRNA 表达谱。利用实时定量 PCR(RT-qPCR)技术,在另一个独立队列(FT1D 受试者 n = 35、T1D 受试者 n = 70 和对照组 n = 100)中筛选出 7 个异常表达的 circRNA,以确定其表达水平。通过生物信息学分析预测了circRNA的生物学功能、circRNA-miRNA-mRNA网络和编码潜力:结果:在 FT1D 和 T1D 中总共发现了 145 个差异表达的 circRNA,其中 63 个上调,82 个下调。在确定表达水平的 7 个异常表达的 circRNA 中,成功验证了 Hsa_circRNA_038288、hsa_circRNA_104405 和 hsa_circRNA_405498。生物信息学分析表明,大部分 circRNA 的母基因都富集在 RNA 转运、泛素介导的蛋白水解和病灶粘附等信号通路中。Hsa_circRNA_038288 似乎在与免疫调节和糖尿病相关的 51 个 circRNA-miRNA-mRNA 信号通路中发挥作用。此外,hsa_circRNA_038288可能具有编码潜力,并参与FT1D和T1D的进展:结论:在 FT1D 和 T1D 患者之间发现了免疫细胞衍生 circRNA 的显著差异,为区分 FT1D 和 T1D 的分子机制提供了新的视角。
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Differences in Immune Cell-Derived Circular RNA Between Fulminant Type 1 Diabetes and Type 1 Diabetes

Aims

Circular RNAs (circRNAs) are associated with fulminant type 1 diabetes (FT1D) and type 1 diabetes (T1D). However, the differences in circRNAs between FT1D and T1D remain unclear. Our objective is to identify peripheral blood mononuclear cells (PBMCs)-derived circRNAs in FT1D and T1D and explore their potential functions.

Materials and methods

PBMCs were extracted from six patients with FT1D and age-, sex-, and duration-matched T1D patients. The Arraystar Human circRNA Array was utilised to obtain circRNA expression profiles. Seven aberrantly expressed circRNAs were selected for determining expression levels in another independent cohort (FT1D subjects n = 35, T1D subjects n = 70, and controls n = 100) using real-time quantitative PCR (RT-qPCR). Biological functions, circRNA-miRNA-mRNA networks, and the coding potential of circRNAs were predicted through bioinformatics analysis.

Results

In total, 145 differentially expressed circRNAs were identified in FT1D and T1D, with 63 upregulated and 82 downregulated circRNAs. Hsa_circRNA_038288, hsa_circRNA_104405, and hsa_circRNA_405498 were successfully validated among the 7 aberrantly expressed circRNAs selected to determine expression levels. Bioinformatics analysis revealed that majority of the parent genes of circRNAs are enriched in signalling pathways such as RNA transport, ubiquitin-mediated proteolysis, and focal adhesion. Hsa_circRNA_038288 appears to play a role in 51 circRNA-miRNA-mRNA signalling pathways associated with immune regulation and diabetes. Additionally, hsa_circRNA_038288 potentially exhibits coding potential and is involved in the progression of both FT1D and T1D.

Conclusions

Significant differences in immune cell-derived circRNAs were found between FT1D and T1D patients, offering novel insights into the molecular mechanisms that distinguish FT1D from T1D.

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来源期刊
Diabetes/Metabolism Research and Reviews
Diabetes/Metabolism Research and Reviews 医学-内分泌学与代谢
CiteScore
17.20
自引率
2.50%
发文量
84
审稿时长
4-8 weeks
期刊介绍: Diabetes/Metabolism Research and Reviews is a premier endocrinology and metabolism journal esteemed by clinicians and researchers alike. Encompassing a wide spectrum of topics including diabetes, endocrinology, metabolism, and obesity, the journal eagerly accepts submissions ranging from clinical studies to basic and translational research, as well as reviews exploring historical progress, controversial issues, and prominent opinions in the field. Join us in advancing knowledge and understanding in the realm of diabetes and metabolism.
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