Objective: Aberrant microRNAs (miRNAs) play vital roles in various human diseases, including atherosclerosis (AS). MiR-647 expression was highly elevated in AS samples. Therefore, this study aimed at exploring the role and mechanism of miR-647 on AS progression.
Patients and methods: Human aorta vascular smooth muscle cells (HA-VSMCs) were treated with oxidized modified low-density lipoprotein (ox-LDL) to establish the AS model in vitro. The qRT-PCR assay was used to detect the expression of miR-647 and PTEN mRNA. The levels of PTEN protein, PI3K, AKT, p-PI3K, and p-AKT were measured using Western blot. Cell proliferation and migration were determined by Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. The target of miR-647 was verified using the dual-luciferase reporter assay.
Results: Our data supported that miR-647 was upregulated and PTEN was downregulated in the serum of AS patients and ox-LDL-treated HA-VSMCs. The proliferation and migration of ox-LDL-treated HA-VSMCs were promoted by miR-647 overexpression or PTEN knockdown, while they were suppressed following miR-647 depletion or high PTEN expression. Moreover, PTEN was a direct target of miR-647. PTEN antagonized miR-647-mediated regulatory effects on cell proliferation and migration. Additionally, the PI3K/AKT signaling pathway was involved in miR-647/PTEN-mediated regulation in ox-LDL-treated HA-VSMCs.
Conclusions: MiR-647 promoted the proliferation and migration of ox-LDL-treated HA-VSMCs at least partly by targeting the PTEN/PI3K/AKT pathway. Targeting miR-647 may be a promising method for AS treatment.