Downregulation of miR-637 promotes vascular smooth muscle cell proliferation and migration via regulation of insulin-like growth factor-2

Abstract

Background: Dysregulation of the proliferation and migration of vascular smooth muscle cells (VSMCs) is a crucial cause of atherosclerosis. MiR-637 exerts an antiproliferative effect on multiple human cells. Its impact on atherosclerosis remains largely unexplored. Methods: Real-time PCR was used to determine miR-637 expression in samples from atherosclerosis patients and animal models. Its expression in VSMC dysfunction models (induced by ox-LDL) was also measured. The proliferation and migration of VSMCs were respectively tested using CCK-8 and Transwell assays, and apoptosis was measured using flow cytometry. The Targetscan database was used to predict the target genes of miR-637. Interaction between miR-637 and the potential target gene was validated via real-time PCR, western blotting and a luciferase reporter assay. Results: MiR-637 expression was significantly lower in atherosclerosis patient and animal model samples. It also decreased in a dose-and time-dependent manner in animal models with ox-LDL-induced atherosclerosis. Transfection with miR-637 mimics suppressed the proliferation and migration of VSMCs while promoting apoptosis, while transfection with miR-637 inhibitors had the opposite effects. We also validated that insulin-like growth factor-2 (IGF-2), a crucial factor in the pathogenesis of atherosclerosis, serves as a target gene for miR-637. Conclusion: MiR-637 targeting IGF-2 contributes to atherosclerosis inhibition and could be a potential target for this disease.

A circular RNA, circUSP36, accelerates endothelial cell dysfunction in atherosclerosis by adsorbing miR-637 to enhance WNT4 expression

“…Through application of the circInteractome database, miR-637 was predicted to be a target of circUSP36. In view of the inhibitory role of miR-637 in atherosclerosis [ 52 ], we selected miR-637 as a research object in subsequent explorations of the molecular mechanism. Luciferase reporter gene and RNA pull-down assays validated that miR-637 directly binds to circUSP36.…”

Dysregulation of miR-637 serves as a diagnostic biomarker in patients with carotid artery stenosis and predicts the occurrence of the cerebral ischemic event

“…It is worth noting that miR-637 was marked downregulated in 86 patients with atherosclerosis, which is a putative mechanism of CAS [ 18 ]. Downregulation of miR-637 is involved in atherosclerosis and promotes the proliferation and migration of vascular smooth muscle cells by regulating insulin-like growth factor 2 [ 36 ]. In patients with essential hypertension, miR-637 is typically reduced [ 37 ].…”

Eplerenone inhibits oxidized low-density lipoprotein-induced proliferation and migration of vascular smooth muscle cells by downregulating GPER expression

“…20 An increasing number of studies have reported that ox-LDL exerts a promotion effect in the development of AS by stimulating the proliferation of VSMCs within the vessel wall. 21,22 Therefore, agents blocking or inhibiting proliferation and migration of VSMCs induced by ox-LDL may contribute to the identification of therapeutic strategies. Eplerenone is a newly found novel selective aldosterone receptor antagonist.…”