Putative Novel miR-1133 Is Associated with Oxidative Stress in Hyperglycemia-Induced Endothelial Cells.

Background: Diabetes mellitus is characterized by chronic hyperglycemia, which promotes oxidative stress and endothelial dysfunction. MicroRNAs (miRNAs) have emerged as important regulators of diabetic vascular complications. Our previous RNA-sequencing study identified putative novel miR-1133 as an upregulated miRNA in hyperglycemia-induced human umbilical vein endothelial cells (HUVECs). This study aimed to investigate the potential involvement of putative novel miR-1133 in oxidative stress in hyperglycemia-induced HUVECs. Methods: Functional enrichment and protein-protein interaction (PPI) network analyses were performed to identify biologically relevant predicted target genes of putative novel miR-1133. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) was selected for further investigation because it was identified as a hub gene in the PPI network and was involved in the enriched PI3K/Akt signaling pathway. HUVECs were exposed to high glucose (33.3 mM) to establish an in vitro hyperglycemic model, and the effects of transfection with putative novel miR-1133 inhibitor on PIK3CA expression and oxidative stress markers were evaluated. Results: Bioinformatic analyses identified PIK3CA as a hub gene among the predicted targets of putative novel miR-1133 and identified the PI3K/Akt signaling pathway as significantly enriched. Experimentally, hyperglycemia significantly reduced PIK3CA expression, whereas putative novel miR-1133 inhibitor transfection increased PIK3CA expression. Furthermore, putative novel miR-1133 inhibitor transfection was associated with reduced reactive oxygen species and 8-hydroxy-2'-deoxyguanosine levels, together with increased superoxide dismutase 1 (SOD1) mRNA expression and total SOD activity. Conclusions: Transfection with putative novel miR-1133 inhibitor was associated with increased PIK3CA expression and reduced oxidative stress markers in hyperglycemia-induced endothelial cells. Together, bioinformatic and experimental findings support an association between putative novel miR-1133 inhibitor transfection, PIK3CA expression, and oxidative stress under hyperglycemic conditions. Further studies are required to validate the direct interaction between putative novel miR-1133 and PIK3CA and to determine the relevance of these findings in vivo.