Circular RNA circUBR4 regulates ox-LDL-induced proliferation and migration of vascular smooth muscle cells through miR-185-5p/FRS2 axis.

Abstract

Circular RNAs (circRNAs) have been reported to play vital roles in atherosclerosis. However, the precise roles of circUBR4 in atherosclerosis remain unclear. The purpose of this study is to investigate the regulatory roles of circUBR4 in atherosclerosis. The expression levels of circUBR4, miR-185-5p, and Fibroblast growth factor receptor substrate 2 (FRS2) were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) assay. Human vascular smooth muscle cells (VSMCs) were treated with oxidized low-density lipoprotein (ox-LDL) to mimic atherosclerosis condition in vitro. Cell proliferation was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), colony-forming, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Wound healing and transwell assays were used to assess cell migration. The interaction relationship between miR-185-5p and circUBR4 or FRS2 was confirmed by dual-luciferase reporter and RNA pull-down assays. CircUBR4 was overexpressed in atherosclerosis patients and VSMCs treated with ox-LDL, and the knockdown of circUBR4 abolished ox-LDL-induced enhanced effects on the proliferation and migration of VSMCs. MiR-185-5p, interacted with FRS2, was a target of circUBR4 in VSMCs. The silencing of miR-185-5p reversed the effects caused by circUBR4 knockdown on ox-LDL-induced VSMCs. In addition, overexpression of miR-185-5p suppressed the proliferation and migration of VSMCs by targeting FRS2. CircUBR4 contributed to ox-LDL-induced VSMC proliferation and migration through up-regulating FRS2 via miR-185-5p.

• Authors: Chen Sun, Jinliang Li, Ying Li, Li Li, Guopeng Huang
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 476 Issue 11 Pg. 3899-3910 (Nov 2021) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 34159479 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Adaptor Proteins, Signal Transducing
• FRS2 protein, human
• Lipoproteins, LDL
• MIRN185 microRNA, human
• Membrane Proteins
• MicroRNAs
• RNA, Circular
• oxidized low density lipoprotein

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Apoptosis (drug effects)
• Atherosclerosis (genetics, metabolism, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Humans
• Lipoproteins, LDL (pharmacology)
• Membrane Proteins (metabolism)
• MicroRNAs (genetics)
• Muscle, Smooth, Vascular (drug effects, metabolism, pathology)
• RNA, Circular (genetics, metabolism)
• Signal Transduction