Potential Target miR-455 Delaying Arterial Stenosis Progression Through PTEN

Ruoran Lin; Junyuan Lv; Lei Wang; Xuan Li; Jing Zhang; Weifeng Sun; Xiaoyun Hu; Shijie Xin

doi:10.3389/fcvm.2021.611116

Potential Target miR-455 Delaying Arterial Stenosis Progression Through PTEN

Front Cardiovasc Med. 2021 Feb 23:8:611116. doi: 10.3389/fcvm.2021.611116. eCollection 2021.

Authors

Ruoran Lin¹, Junyuan Lv², Lei Wang¹, Xuan Li¹, Jing Zhang³, Weifeng Sun⁴, Xiaoyun Hu³, Shijie Xin¹

Affiliations

¹ Department of Vascular Surgery, The First Hospital of China Medical University, Shenyang, China.
² Department of Breast and Thyroid Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
³ Liaoning Key Laboratory of Molecular Tumor Drug Development and Evaluation, Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.
⁴ Department of Gastrointestinal Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

Abstract

Background: Vascular smooth muscle cells (VSMC) underwent phenotypic switching upon stimulation signals, and this is the prerequisite for their proliferation and migration. Previous work revealed that miR-455 may be involved in vascular stenosis. Thus, this study aimed to explore potential targets and mechanisms underlying the dynamics of miR-455 in vascular stenosis. Methods: miR-455 and PTEN expression levels were studied in normal and stenosis tissue, as well as in VSMC in proliferation model. Manipulating miR-455 expression levels was achieved by transfection of either miR-455 mimic or inhibitor, and its effect on cell proliferation was studied by CCK-8 assay. Its effect on gene expression was studied by RT-qPCR and western blot. The expression regulation mechanism was studied by luciferase reporter system. Finally, the effect of miR-455 on regulating vascular stenosis was studied using a rat balloon-injured carotid artery stenosis model. Results: High expression levels of miR-455 were detected in both stenosis arterial tissues and VSMC proliferation models. In contrast, the expression levels of PTEN were downregulated in these systems. miR-455 transfected VSMC showed higher levels of proliferation and decreased levels of PTEN. Potential binding sites between miR-455 and PTEN 3'UTR were predicted and confirmed. NF-kB p65 was found to bind directly on miR-455 promoter region and regulate its transcription. The progression of arterial stenosis could be delayed by introducing miR-455 antagomir. Conclusions: The p65/miR-455/PTEN signaling pathway plays a crucial role in regulating VSMC proliferation and vascular stenosis. This indicated that miR-455 is a novel target that would help improve treatment outcomes in patients suffering from vascular stenosis.

Keywords: miR-455; phenotype; proliferation; stenosis; vascular smooth muscle cell.