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Diagnostic Roles of circXPNPEP3 as Biomarker for Diabetic Nephropathy

Miao Liu,Qiunan Zhan,Junjun Zhu,Junli Zhao,Danyan Min

Published 2025 in Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy

ABSTRACT

Background Diabetic nephropathy (DN) is a common chronic microvascular complication of diabetes mellitus (DM). Circular RNAs (circRNAs) have emerged as ideal biomarkers for various diseases. Recent studies have shown that circXPNPEP3 is upregulated in high glucose‐induced human umbilical vein endothelial cells. In this study, we aimed to examine the expression levels of circXPNPEP3 in the serum of patients with DN and to evaluate its diagnostic potential for this condition. Methods The expression levels of circXPNPEP3 in DN tissues and serum were detected using quantitative real-time polymerase chain reaction (qRT-PCR). DN was confirmed by biopsy or clinically defined as a urine albumin/creatinine ratio (uACR) > 30 mg/g or an estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2. The association between circXPNPEP3 expression levels and the clinical features of patients with DN was investigated. Using healthy individuals as controls, the diagnostic value of circXPNPEP3 for DN was evaluated by receiver operating characteristic (ROC) curve analysis. Finally, a potential RNA-interaction-network involving circXPNPEP3 was constructed using bioinformatics approaches. Results The expression levels of circXPNPEP3 were significantly upregulated in both DN tissues and serum compared to those in non-DN tissues and serum from healthy controls. The dysregulation of circXPNPEP3 was significantly correlated with albuminuria categories and glomerular filtration rate (GFR) categories. Serum expression of circXPNPEP3 distinguished patients with DN from controls, yielding an area under the ROC curve (AUC) of 0.8389, with a sensitivity of 70.59% and a specificity of 86.27%. Finally, hsa-miR-135b-5p, hsa-miR-135a-3p, and hsa-miR-1237-3p were predicted to be potential targets of circXPNPEP3 in DN, and a competing endogenous RNA (ceRNA) network involving circXPNPEP3 was constructed based on bioinformatic predictions. Conclusion CircXPNPEP3 is upregulated in DN tissues and serum. Its elevated expression in serum shows promise as a non-invasive diagnostic biomarker for DN.

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