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Published on: May 2, 2025
Diagnostic Roles of circXPNPEP3 as Biomarker for Diabetic Nephropathy
Miao Liu1, Qiunan Zhan1, Junjun Zhu1
1Department of Nephrology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai Pudong New District Zhoupu Hospital, Shanghai, People's Republic of China.
Insights
Circular RNA XPNPEP3 (circXPNPEP3) is elevated in diabetic nephropathy (DN) tissues and serum. This finding suggests circXPNPEP3 is a promising non-invasive biomarker for diagnosing DN.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM).
- Circular RNAs (circRNAs) are emerging as significant biomarkers in disease diagnostics.
- Previous research indicated circXPNPEP3 upregulation in high glucose conditions.
Purpose of the Study:
- To investigate circXPNPEP3 expression levels in the serum of DN patients.
- To assess the diagnostic potential of circXPNPEP3 for DN.
- To explore the relationship between circXPNPEP3 and clinical features of DN.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) was used to measure circXPNPEP3 expression in tissues and serum.
- DN diagnosis was confirmed via biopsy or clinical criteria (uACR > 30 mg/g or eGFR < 60 mL/min/1.73 m²).
- Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic value of serum circXPNPEP3.
Main Results:
- Serum and tissue circXPNPEP3 levels were significantly higher in DN patients compared to controls.
- circXPNPEP3 expression correlated with albuminuria and glomerular filtration rate (GFR) categories.
- Serum circXPNPEP3 demonstrated a diagnostic AUC of 0.8389, with 70.59% sensitivity and 86.27% specificity for DN detection.
Conclusions:
- CircXPNPEP3 is upregulated in both DN tissues and serum.
- Elevated serum circXPNPEP3 shows potential as a non-invasive biomarker for DN diagnosis.
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.

