Metformin Alters the MicroRNA Profile of High Glucose-Induced Human Umbilical Vein Endothelial Cells

MicroRNAs (miRNAs) contribute to the progression of vascular complications in diabetes. Metformin has been shown to protect against endothelial dysfunction in diabetes; however, it remained unclear whether this effect was mediated through the modulation of miRNAs. To gain insight into the effects of metformin on miRNA profile in endothelial cells treated with high glucose, we utilised next gene sequencing (NGS) and further conducted the bioinformatic analyses to explore the associated target genes and pathways. NGS revealed 19 miRNAs with differential expression, including nine downregulated and 10 upregulated miRNAs. Gene ontology highlighted molecular functions and biological processes such as ErbB-2 class receptor binding and receptor activity regulation, which are crucial in mediating the involvement of metformin in diabetes-induced oxidative stress and apoptosis. Kyoto Encyclopedia of Genes and Genomes pathway analysis connected these miRNAs to diabetes-related pathways, such as type II diabetes mellitus and phosphatidylinositol signaling system. Furthermore, network analysis of protein interaction identified important genes, such as glyceraldehyde-3-phosphate dehydrogenase, sirtuin 1 and Jun proto-oncogene as hub genes in modulating oxidative stress and apoptosis. In conclusion, this study elucidates how metformin exerts its protective effects on diabetic vascular endothelial dysfunction by modulating miRNAs. These findings could help develop more targeted therapeutic interventions for diabetes.