Exploring the Impact of miR-10a, miR-141, miR-200a and miR-3658 on Cystinuria

Introduction: Cystinuria is an inherited disorder characterized by impaired proximal tubular reabsorption of cystine, resulting in recurrent cystine stone formation. Mutations in the SLC3A1 and SLC7A9 genes are the main genetic causes of the disease, while variants in PBX1 have also been associated with cystinuria in specific populations. Despite advances in understanding its molecular basis, cystinuria remains clinically heterogeneous, making disease progression and prognosis difficult to predict. This study aimed to investigate circulating microRNAs (miRNAs) as potential molecular biomarkers, characterize their expression profile in patients with cystinuria, and evaluate their association with clinical indicators of disease severity. Methods: The study group included 16 patients with a clinically established diagnosis of cystinuria, while the control group consisted of 11 healthy individuals without a history of nephrolithiasis. Candidate miRNAs were selected based on their predicted regulatory interactions with genes implicated in cystinuria pathogenesis. Eight microRNAs (miR-29a-3p, miR-29b-3p, miR-29c-3p, miR-1207-3p, miR-10a-3p, miR-3658, miR-141-3p, and miR-200a-3p) were analyzed by quantitative real-time PCR (qPCR). Results: Among the eight miRNAs evaluated, miR-10a, miR-141, miR-200a, and miR-3658 were significantly downregulated in patients with cystinuria compared with healthy controls. Higher expression levels of miR-10a, miR-141, and miR-200a were significantly associated with a greater number of previous surgical procedures (p < 0.05). Additionally, increased miR-10a expression was associated with impaired renal function, defined as serum creatinine levels above 1.2 mg/dL. Conclusions: miR-10a, miR-141, miR-200a, and miR-3658 were significantly downregulated in patients with cystinuria compared with healthy controls. Within the cystinuria cohort, higher expression of miR-10a was associated with impaired renal function, whereas increased expression of miR-10a, miR-141, and miR-200a correlated with a greater number of surgical interventions, suggesting a potential relationship with disease severity. Further studies in larger, genetically characterized cohorts are warranted to clarify the biological role and clinical utility of these miRNAs as biomarkers of cystinuria.