CircEGLN1 alleviates calcium oxalate-induced renal injury via miR-212-5p/STARD7 axis, offering a potential strategy for kidney stone prevention

Renal tubular injury driven by calcium oxalate (CaOx)-induced oxidative stress constitutes a major contributor to kidney stone formation, while the regulatory role of circRNAs in this process remains poorly characterized. Through high-throughput circRNA Sequencing using a calcium oxalate monohydrate (COM)-induced HK-2 cell model, we identified the evolutionarily conserved circEGLN1 as a critical protective factor against oxidative damage. Functional assays in a CaOx nephrolithiasis mouse model and in COM-treated cells, including rescue experiments, demonstrated that circEGLN1 reduces oxidative injury by sequestering miR-212-5p, thereby upregulating STARD7 and mitigating oxidative stress. In vivo experiments revealed that circEGLN1 overexpression attenuates oxidative stress and inhibits crystal deposition in renal tissues via miR-212-5p targeting, providing protection against CaOx-induced injury. RNA fluorescence in situ hybridization analysis of clinical specimens showed significantly lower circEGLN1 expression in stone-containing tissues than in non-stone normal counterparts, indicating its pathophysiological relevance. This study elucidates the circEGLN1/miR-212-5p/STARD7 axis as a novel regulatory mechanism for oxidative injury in nephrolithiasis. These findings not only advance the understanding of ncRNA-mediated renal protection but also highlight circEGLN1 as a promising therapeutic target for preventing CaOx-induced kidney stone formation.

Calcium oxalate nephrolithiasis; Oxidative injury; STARD7; ceRNA; circEGLN1.