Emerging role of hsa_circ_0000652, hsa-miR-21, SMAD2, and Foxo1 in type 2 diabetes mellitus pathogenesis

Abstract

Background

Diabetes mellitus (DM) is considered a metabolic disorder widely distributed worldwide. Optimal options of treatment and their related mechanisms are still unclear despite intense investigations. MicroRNAs (miRNAs) are small noncoding that control molecular signaling pathways in various diseases including DM. miR-21 has a role in multiple biological processes as apoptosis, and proliferation of the cell. The aim of the present work is to investigate the epigenetic control of DM pathogenesis.

Methods

The current study enrolled 30 healthy controls and 30 patients diagnosed with type II diabetes (T2DM). miR-21, hsa_circ_0000652, Foxo1, and SMAD2 expressions were evaluated by qRT-PCR. Moreover, Bioinformatics analysis of hsa_circ_0000652 and its targeted pathways was investigated.

Results

hsa_circ_0000652 and miR-21 were up-regulated in T2DM. hsa_circ_0000652 restricts the inhibitory effect of miR-21 of its targeted genes (SMAD2, Foxo1) that were up regulated in diabetic patients (P value <0.001), miR-21 was significantly correlated with hsa_circ_0000652, SMAD2, and Foxo1 (p-values = 0.022, 0.003, and < 0.001, respectively). ROC analysis of hsa-miR-21 and hsa_circ_0000652 revealed that they are significant diagnostic factors for T2DM (P value <0.001, AUC =0.98, 0.927), they also represent a significant risk factor for occurrence of T2DM.

Conclusion

hsa-miR-21 and hsa_circ_0000652 are potent regulators in DM pathogenesis and could be novel therapeutic targets for treatment and prevention of DM.