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Published on: December 21, 2016
Identification of hsa_circRNA_100632 as a novel molecular biomarker for fulminant type 1 diabetes
Wenfeng Yin1, Shuoming Luo1, Junlin Qiu1
1National 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.
Insights
Circular RNAs (circRNAs) show altered expression in fulminant type 1 diabetes (FT1D). Hsa_circRNA_100632 is a potential diagnostic biomarker for FT1D, distinguishing it from controls and type 1 diabetes.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in diabetes pathogenesis.
- The specific role of circRNAs in fulminant type 1 diabetes (FT1D) remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression profiles and diagnostic potential of circRNAs in FT1D.
- To identify specific circRNAs associated with FT1D and explore their potential functions.
Main Methods:
- CircRNA expression profiling using microarrays in peripheral blood mononuclear cells (PBMCs) from FT1D patients and controls.
- Validation of candidate circRNAs via quantitative real-time polymerase chain reaction (qRT-PCR) in an independent cohort.
- Bioinformatics analysis for pathway and interaction prediction (circRNA-miRNA-mRNA).
Main Results:
- 13 circRNAs were upregulated and 13 downregulated in FT1D PBMCs.
- Hsa_circRNA_100632 was significantly upregulated in both FT1D and type 1 diabetes (T1D) groups.
- Hsa_circRNA_100632 demonstrated strong diagnostic capability for FT1D versus controls (AUC 0.846) and FT1D versus T1D (AUC 0.726).
Conclusions:
- Aberrant circRNA expression is evident in PBMCs of FT1D patients.
- Hsa_circRNA_100632 emerges as a promising diagnostic biomarker for FT1D.
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; P<0.0001] as well as between patients with FT1D and patients with T1D (AUC 0.726; 95% CI 0.633-0.820; P<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.
