Systematic validation of miR-503-5p abnormal expression in diabetic vascular complications: a meta-analysis and exploration of its targeted regulatory mechanism in retinopathy.

BACKGROUND: Diabetic vascular complications are major health concerns. MicroRNAs (miRNAs) are implicated in their pathogenesis. This study aimed to evaluate the abnormal expression of miR-503-5p in diabetic vascular complications and explore its regulatory mechanisms in diabetic retinopathy. METHODS: Studies on miR-503-5p expression in diabetic vascular complications were selected from PubMed, Embase, Web of Science, Cochrane, and Scopus databases. Experimental validation was carried out utilizing human retinal pigment epithelial cells (ARPE-19) that were subjected to a high glucose (HG) environment. miR-503-5p expression, cell proliferation, apoptosis, inflammatory cytokines, and oxidative stress markers were measured. RESULTS: The meta-analysis showed miR-503-5p was upregulated overall in diabetic vascular complications (SMD = 0.71, 95% CI: -2.21 to 3.64). Subgroup analysis showed that miR-503-5p expression was significantly increased in cell samples (SMD = 5.84, 95% CI: 2.40 to 9.27), and in major vascular complications (SMD = 2.89, 95% CI: 0.35 to 5.44). High miR-503-5p could distinguish diabetic retinopathy from healthy controls (AUC = 0.918, sensitivity = 81.2%, specificity = 92.7%). HG upregulated miR-503-5p in ARPE-19 cells. miR-503-5p inhibitor linked to increased proliferation, reduced apoptosis, and modulated inflammatory and oxidative stress responses. CONCLUSIONS: MiR-503-5p was significantly upregulated in diabetic vascular complications, particularly in cell samples and major vascular complications. MiR-503-5p may serve as a diagnostic biomarker for diabetic retinopathy. The elevated levels of miR-503-5p in ARPE-19 cells under high glucose conditions were associated with increased inflammation, oxidative stress, and apoptosis, as well as decreased cell proliferation.