Introduction: Data from the CEO database shows microRNA (miR) -28-3p levels are elevated in diabetic patients. Nevertheless, the role of miR-28-3p in peripheral artery disease with diabetes have not been investigated.

Material and methods:
The level of miR-28-3p, CXXC5, CXXC-type zinc finger protein 5, and CXXC5’s downstream molecules as well as endothelial function were investigated. Dual luciferase analyses were used to confirm the binding site of miR-28-3p and CXXC5.

Results: Under high-glucose condition, miR-28-3p expression is increased whereas CXXC5 expression is downregulated. Overexpression of miR-28-3p increased cell apoptosis and inhibited cell proliferation, migration, and vessel formation, whilst inhibiting its expression had the opposite effect. The overexpression and inhibition of miR-28-3p could also influence both the mRNA and protein levels of CXXC5 and its known downstream molecules. Analysis of bioinformatics data revealed a potential binding site for miR-28-3p and CXXC5. Dual luciferase analyses demonstrated that miR-28-3p suppressed CXXC5 expression by targeting the 3'-untranslated region (3'-UTR) of CXXC5. Following that, we overexpressed both miR-28-3p and CXXC5. The level of CXXC5 and its known downstream signaling molecules decreased with miR-28-3p overexpression alone. As anticipated, co-overexpression of miR-28-3p and CXXC5 partially reversed the effect of miR-28-3p mimics.

Conclusion: These findings indicated that miR-28-3p regulated high glucose-induced endothelial dysfunction by targeting CXXC5.

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