LncRNA VCAN‐AS1 serves as a diagnostic biomarker and drives pathogenesis in diabetic nephropathy via the miR‐205‐5p/VEGFA axis

Aims Diabetic nephropathy (DN) represents a major complication of diabetes mellitus (DM) with limited early diagnostic biomarkers. This study investigated the clinical significance and molecular mechanism of long non‐coding RNA (lncRNA) VCAN‐AS1 in DN pathogenesis. Methods The patients with diabetes mellitus, including 85 with DN and 66 without nephropathy, were enrolled, along with 62 healthy controls. Serum VCAN‐AS1 levels were detected using qRT‐PCR. Clinical parameters and renal injury markers were analysed for correlations with VCAN‐AS1. In vitro, high glucose‐treated human renal tubular cells (HK‐2) underwent genetic interventions including VCAN‐AS1 knockdown and miR‐205‐5p inhibition. Functional assessments encompassed cell viability, oxidative stress, fibrosis and inflammation. Dual‐luciferase reporter assays validated molecular interactions. Results Serum VCAN‐AS1 expression showed a progressive increase across healthy controls, diabetes mellitus patients and DN patients. It exhibited strong diagnostic efficacy for DN with an AUC of 0.879. Elevated VCAN‐AS1 correlated with deteriorated renal function parameters. VCAN‐AS1 was identified as an independent risk factor for diabetes mellitus progression to DN. High glucose exposure up‐regulated VCAN‐AS1 in HK‐2 cells, promoting cellular injury phenotypes. Rescue experiments confirmed that miR‐205‐5p inhibition reversed the protective effects of VCAN‐AS1 knockdown. Mechanistically, VCAN‐AS1 directly bound miR‐205‐5p, suppressing its expression and consequently enhancing vascular endothelial growth factor A (VEGFA) expression. Conclusions VCAN‐AS1 serves as a potential diagnostic biomarker for DN and promotes disease pathogenesis through the miR‐205‐5p/VEGFA axis, highlighting its potential as a therapeutic target.