鉴定 hsa_circRNA_100632 作为暴发性 1 型糖尿病的新型分子生物标志物。
Identification of hsa_circRNA_100632 as a novel molecular biomarker for fulminant type 1 diabetes.
机构信息
National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
出版信息
Front Immunol. 2023 Feb 23;14:1075970. doi: 10.3389/fimmu.2023.1075970. eCollection 2023.
OBJECTIVE
Circular RNAs (circRNAs) are associated with diabetes, but their role in fulminant type 1 diabetes (FT1D) is unclear. Thus, we characterized the role of circRNAs in FT1D.
RESEARCH DESIGN AND METHODS
CircRNA expression profiles were detected in peripheral blood mononuclear cells (PBMCs) of five FT1D patients and five controls using a circRNA microarray. An independent cohort comprised of 40 FT1D cases, 75 type 1 diabetes (T1D) cases, and 115 controls was used to verify the circRNAs using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman's correlation analysis and receiver operating characteristic (ROC) curve analysis were performed to determine the clinical diagnostic capability of circRNAs. Bioinformatics was used to identify potential biological functions and circRNA-miRNA-mRNA interactions.
RESULTS
There were 13 upregulated and 13 downregulated circRNAs in PBMCs of patients with FT1D. Five circRNAs were further verified in a second cohort. Hsa_circRNA_100632 was significantly upregulated in the FT1D and T1D groups. Hsa_circRNA_100632 was differentiated between patients with FT1D and controls [area under the curve (AUC) 0.846; 95% CI 0.776-0.916; <0.0001] as well as between patients with FT1D and patients with T1D (AUC 0.726; 95% CI 0.633-0.820; <0.0001). Bioinformatics analysis showed that hsa_circRNA_100632 may be involved in 47 circRNA-miRNA-mRNA signaling pathways associated with diabetes.
CONCLUSIONS
CircRNAs were aberrantly expressed in PBMCs of patients with FT1D, and hsa_circRNA_100632 may be a diagnostic marker of FT1D.
目的
环状 RNA（circRNAs）与糖尿病有关，但它们在暴发性 1 型糖尿病（FT1D）中的作用尚不清楚。因此，我们研究了 circRNAs 在 FT1D 中的作用。
研究设计和方法
使用 circRNA 微阵列检测了五例 FT1D 患者和五名对照者外周血单核细胞（PBMCs）中的 circRNA 表达谱。一个包含 40 例 FT1D 病例、75 例 1 型糖尿病（T1D）病例和 115 名对照者的独立队列用于使用定量实时聚合酶链反应（qRT-PCR）验证 circRNAs。进行 Spearman 相关分析和接受者操作特征（ROC）曲线分析，以确定 circRNAs 的临床诊断能力。使用生物信息学方法鉴定潜在的生物学功能和 circRNA-miRNA-mRNA 相互作用。
结果
FT1D 患者 PBMCs 中有 13 个 circRNAs 上调，13 个 circRNAs 下调。在第二个队列中进一步验证了五个 circRNAs。Hsa_circRNA_100632 在 FT1D 和 T1D 组中显著上调。Hsa_circRNA_100632 能够区分 FT1D 患者与对照组（曲线下面积（AUC）0.846；95%CI 0.776-0.916；<0.0001）以及 FT1D 患者与 T1D 患者（AUC 0.726；95%CI 0.633-0.820；<0.0001）。生物信息学分析表明，hsa_circRNA_100632 可能参与了 47 个与糖尿病相关的 circRNA-miRNA-mRNA 信号通路。
结论
FT1D 患者 PBMCs 中存在 circRNA 异常表达，hsa_circRNA_100632 可能是 FT1D 的诊断标志物。
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