63Identification of insulin signaling pathway-related circulating circRNAs as biomarkers of type 2 diabetes

Abstract

Abstract Background The underlying molecular mechanism of type 2 diabetes (T2D) is that abnormalities occur in the insulin signaling pathway. Circular RNAs (circRNAs) are involved in the development of diseases by regulating gene expression and become promising novel biomarkers for diseases. This study systematically screened and validated the insulin signaling pathway-related circulating circRNAs in T2D. Methods circRNA expression profiles were screened by microarray between five T2D patients and five healthy controls. The candidate circRNAs were then selected from those differently expressed circRNAs whose potential target miRNAs are involved in regulating key genes in the isulin signaling pathway. The expression of candidate circRNAs were validated in a second sample with 20 T2D cases and 20 controls by real-time quantitative PCR. Eventually, the association between circRNAs and T2D and their clinical significance were further confirmed in a large independent sample, including 103 T2D cases, 93 controls and 80 individuals with impaired fasting glucose (IFG) as prediabetes cases. Results Four circRNAs including hsa_circ_0063425, hsa_circ_0056891, hsa_circ_0078166 and hsa_circ_0071336 were validated by RT-qPCR. Low expressed circ_0063425, hsa_circ_0056891 and hsa_circ_0071336 were independent predictor of T2D, IFG and insulin resistance. The three-circRNA panel had a high accuracy for diagnosing T2D and IFG, especially when BMI was integrated. Bioinformatics Gene Ontology and pathway analysis confirmed that these circRNAs involve in the regulation of insulin signaling pathway. Conclusion circ_0063425, hsa_circ_0056891 and hsa_circ_0071336 are valuable circulating biomarkers for T2D, and may involve in regulating insulin signaling pathway. Key messages Insulin signaling pathway-related circulating circRNAs were identification as biomarkers of T2D.