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

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.

Role of EZH2-mediated epigenetic modification on vascular smooth muscle in cardiovascular diseases: A mini-review

“…Additionally, the circHECTD1 gene promotes VSMC proliferation and migration ( Feng et al, 2023 ). Silencing EZH2 in VSMCs can reverse the proliferation enhancement effect of circHECTD1 on VSMCs.…”

“…Silencing EZH2 in VSMCs can reverse the proliferation enhancement effect of circHECTD1 on VSMCs. As an important histone modification regulator, EZH2 can be specifically targeted to inhibit circHECTD1 and reduce atherosclerotic plaque formation ( Feng et al, 2023 ). Conversely, mechanical stretch ( Zhong et al, 2022 ) and miR-630 overexpression ( Miao et al, 2022 ) can inhibit EZH2 expression in VSMCs, reducing atherosclerotic lesions ( Figure 2 ).…”