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