Inhibition of microRNA-25 by tumor necrosis factor α is critical in the modulation of vascular smooth muscle cell proliferation.

Atherosclerosis and coronary heart disease are characterized by a hyperplastic neointima and inflammation involving cytokines, such as tumor necrosis factor‑α (TNF‑α). TNF‑α is pleiotropic and mediates inflammation and proliferation in various cell types, such as vascular smooth muscle cells (VSMCs). The molecular mechanism for the pleiotropic effects of TNF‑α has not previously been fully elucidated. The current study identified that the expression of microRNA‑25 (miR‑25), a small noncoding RNA, was reduced in response to TNF‑α signaling in VSMCs. Restored miR‑25 expression inhibited cell proliferation and Ki‑67 expression. The present study indicated that cyclin‑dependent kinase 6 (CDK6) was the direct target gene of miR‑25 using mRNA and protein expression analysis, and luciferase assays. It was also observed that restored CDK6 expression in the miR‑25 mimic‑treated VSMCs partly reduced miR‑25‑mediated VSMC proliferation. In conclusion, miR‑25 is suggested to be important in TNF‑α‑induced abnormal proliferation of VSMCs.