Circ-CHFR modulates the proliferation, migration, and invasion of ox-LDL-induced human aorta vascular smooth muscle cells through the miR-214-3p/PAPPA axis.

Abstract

Circular RNAs (circRNAs) are associated with the pathogenesis of human diseases, including atherosclerosis. Here, we undertook to investigate the biological role and mechanism of circRNA E3 ubiquitin-protein ligase (circ-CHFR) in atherosclerosis. The expression levels of circ-CHFR, miR-214-3p, and pregnancy-associated plasma protein A (PAPPA) were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in human aorta vascular smooth muscle cells (HA-VSMCs) exposed to oxidized low-density lipoprotein (ox-LDL). Cell proliferation, migration, and invasion capabilities were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), and transwell assays, respectively. The relationship between miR-214-3p and circ-CHFR or PAPPA was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Our data showed that circ-CHFR was upregulated in HA-VSMCs after stimulation with ox-LDL. Downregulation of circ-CHFR inhibited the proliferation, migration, and invasion of HA-VSMCs exposed to ox-LDL. Mechanistically, circ-CHFR acted as a miR-214-3p sponge, and miR-214-3p was a molecular mediator of circ-CHFR regulation in ox-LDL-stimulated HA-VSMCs. PAPPA was a miR-214-3p target, and circ-CHFR regulated the expression of PAPPA by sponging miR-214-3p. Moreover, overexpression of miR-214-3p repressed the proliferation, migration, and invasion of ox-LDL-induced HA-VSMCs by decreasing PAPPA expression. Our findings suggest that the circ-CHFR/miR-214-3p/PAPPA axis regulates ox-LDL-induced proliferation, migration, and invasion in HA-VSMCs.

• Authors: Qianqian Lu, Ying Li, Jiaping Lou, Pingzhen Li, Yi Gu, Xianghai Wang
• Journal: Clinical hemorheology and microcirculation (Clin Hemorheol Microcirc) Vol. 80 Issue 4 Pg. 399-412 ( 2022) ISSN: 1875-8622 [Electronic] Netherlands
• PMID: 34842180 (Publication Type: Journal Article)

Chemical References

• Cell Cycle Proteins
• Lipoproteins, LDL
• MIRN214 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• Poly-ADP-Ribose Binding Proteins
• RNA, Circular
• oxidized low density lipoprotein
• CHFR protein, human
• Ubiquitin-Protein Ligases
• Pregnancy-Associated Plasma Protein-A
• PAPPA protein, human

Topics

• Aorta (metabolism, pathology)
• Atherosclerosis (genetics, pathology)
• Cell Cycle Proteins
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Cells, Cultured
• Humans
• Lipoproteins, LDL (metabolism, pharmacology)
• MicroRNAs (genetics, metabolism)
• Muscle, Smooth, Vascular (metabolism)
• Neoplasm Proteins (genetics, metabolism)
• Poly-ADP-Ribose Binding Proteins (metabolism)
• Pregnancy-Associated Plasma Protein-A (metabolism)
• RNA, Circular (genetics)
• Signal Transduction
• Ubiquitin-Protein Ligases