circHECTD1 Promotes the Proliferation and Migration of Human Brain Vascular Smooth Muscle Cells via Interacting with KHDRBS3 to Stabilize EZH2 mRNA Expression

Meina Feng; Wenxian Tu; Qin Zhou; Yuanmin Du; Kang Xu; Yunfeng Wang

doi:10.2147/JIR.S398199

circHECTD1 Promotes the Proliferation and Migration of Human Brain Vascular Smooth Muscle Cells via Interacting with KHDRBS3 to Stabilize EZH2 mRNA Expression

J Inflamm Res. 2023 Mar 24:16:1311-1323. doi: 10.2147/JIR.S398199. eCollection 2023.

Authors

Meina Feng^#¹, Wenxian Tu^#¹, Qin Zhou¹, Yuanmin Du¹, Kang Xu¹, Yunfeng Wang¹

Affiliation

¹ Department of Neurology, Wuhan Brain Hospital, General Hospital of the YANGTZE River Shipping, Wuhan, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: The objective of this paper is to explore the role of circHECTD1 in vascular smooth muscle cells (VSMCs) and atherosclerosis (AS).

Methods: VSMCs were treated with platelet-derived growth factor-BB (PDGF-BB) in vitro, and the level of circHECTD1 was determined using qRT-PCR. Cell proliferation, migration, and invasion were analyzed using CCK8 and transwell assays. Cell apoptosis and cell cycle were analyzed using flow cytometry. The binding interaction between circHECTD1 and KHDRBS3 or EZH2 was investigated using the RIP, RNA pull-down.

Results: CircHECTD1 was upregulated in PDGF-BB-induced VSMCs with a dose-dependent and time-dependent manner. Knockdown of circHECTD1 suppressed VSMCsproliferation and migration and enhanced cell apoptosis in VSMCs, while circHECTD1 overexpression yielded opposite effects. Mechanistically, circHECTD1 could interact with KHDRBS3, thus enhanced the stability of EZH2 mRNA and increased EZH2 protein level. In addition, silencing EZH2 in VSMCs reversed the proliferation-enhancing effect of circHECTD1 overexpression.

Conclusion: Our findings provided providing a potential prognostic and therapy biomarker for AS.

Keywords: EZH2; KHDRBS3; VSMCs; atherosclerosis; circHECTD1.