MiR-193-3p inhibits the malignant progression of atherosclerosis by targeting WDR5

The aberrantly increased proliferation and migration of vascular smooth muscle cells (VSMCs) was critically associated with atherosclerosis (AS) progression. MiR-197-3p has been confirmed to regulate various biological processes, such as tumorigenesis; however, whether miR-197-3p is involved with the pathological development of AS remains largely unknown.

The serum levels of miR-197-3p in AS patients and healthy donors were determined by polymerase chain reaction (PCR) assay. The transfection efficacies of miR-197-3p mimic or inhibitor in VSMCs were evaluated by PCR assay. The effects of miR-197-3p on VSMC proliferation and migration were determined by EdU cell proliferation and Traswell migration assays. Western blotting was conducted to evaluate the effect of miR-197-3p on WDR5 expression in VSMCs.

In the present study, we found that the expression of miR-197-3p was decreased in the serum of AS patients compared to healthy donors. Overexpression of miR-197-3p inhibited the proliferation and migration of VSMCs, while silencing miR-197-3p showed opposite effects. Mechanistical study revealed that WD Repeat Domain 5 (WDR5) was a target of miR-197-3p. Moreover, miR-197-3p was downregulated in VSMCs upon IL6 treatment and inhibited IL6-induced proliferation and migration in VSMCs.

These findings indicate that miR-197-3p could serve as a promising diagnostic marker for AS and that targeting IL6/miR-197-3p/WDR5 axis might be a potential approach to treat AS.