The relation between CircRNA0056618 and type 2 diabetes mellitus and insulin resistance through miRNA-206/PTPn-1 pathway

Abstract

Diabetes mellitus (DM) is a well-known metabolic syndrome characterized by hyperglycemia produced by a defect in insulin synthesis, insulin action, or a combination of the two. The aim of this work was to find out how circular RNA 0056618 (circRNA 0056618) interacts with miRNA-206 to control blood sugar levels in type-2 diabetes mellitus (T2DM), as well as to test the role of PTPN-1 gene expression and protein phosphatase-2 (PP2A), insulin receptor substrate (IRS) protein level in diabetes. Also, whether circRNA 0056618, miRNA-206, PTPN-1, IRS, and PP2A protein could be used as biomarkers for T2DM diagnosis and prognosis. This cross-sectional analytic study was carried out on 110 patients. Participants were divided into two equal groups: patients’ group (T2DM) and control group (normal participants). All participants were subjected to quantitative real-time PCR for assessed RNAs (circRNA 0056618, miRNA-206, and PTPn-1 gene expression), enzyme-linked immunosorbent assay technique for IRS, and PP2A protein levels. The Statistical Package for the Social Sciences (SPSS), version 28 was used to code and enter the data. All data will be presented as means and SDs. Correlations between quantitative variables will be done using Pearson correlation coefficient. Receiver operating characteristic (ROC) curve was constructed with area under the curve (AUC) analysis performed to detect the best cutoff value of significant parameters for detection of cases. P value will be considered significant less than 0.05. There was a significant increase in circRNA 0056618 (P<0.001), PTPN-1 gene expression (P=0.002), and PP2A protein levels (P<0.001) and a significant decrease in miRNA-206 gene expression and IRS protein levels in diabetic cases (P<0.001) when compared with normal controls. There was a negative correlation between circRNA 0056618 and miRNA-206 and a positive correlation between circRNA 0056618 and PTPN-1. IRS at 0.840 showed 94.5% sensitivity and 90.9% specificity and AUC 0.905. PP2A at 0.868, sensitivity 96.4% and specificity 81.8%, and AUC 0.919. ROC curve for circRNA 0056618, at 0.882, sensitivity 89.1% and specificity 87.3%, and AUC 0.932, miRNA-206 at 0.785, sensitivity 85.5% and specificity 85.5%, and AUC 0.869. ROC curve for PTPN-1 at 0.556, sensitivity 67.3% and specificity 67.3%, and AUC 0.669. We concluded that circRNA 0056618, PTPN-1, PP2A, miRNA-206 and IRS are considered diagnostic, predictive biomarkers in T2DM. Future RNA-based therapy approaches may benefit from an understanding of such new pathways.