Hsa_circ_0007765 Promotes Platelet-Derived Growth Factor-BB-Induced Proliferation and Migration of Human Aortic Vascular Smooth Muscle Cells in Atherosclerosis

Cardiovasc Toxicol. 2024 Oct;24(10):1077-1089. doi: 10.1007/s12012-024-09899-6. Epub 2024 Aug 10.

Abstract

Human aortic vascular smooth muscle cells (HA-VSMCs) play vital roles in the pathogenesis of vascular diseases, including Atherosclerosis (AS). Circular RNAs (circRNAs) have been reported to regulate the biological functions of HA-VSMCs. Therefore, this study aimed to explore the role and mechanism of hsa_circRNA_102353 (circ_0007765) in platelet-derived growth factor-BB (PDGF-BB)-induced HA-VSMCs. Circ_0007765, microRNA-654-3p (miR-654-3p), and Fibroblast Growth Factor Receptor Substrate 2 (FRS2) expression were measured using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferative ability, invasion, and migration were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), Transwell, and wound healing assays. CyclinD1, MMP2, and FRS2 protein levels were assessed using a Western blot assay. Binding between miR-654-3p and circ_0007765 or FRS2 was predicted by Circinteractome or TargetScan, and verified using dual-luciferase reporter and RNA pull-down assays. PDGF-BB induced HA-VSMC proliferation, invasion, and migration. Circ_0007765 and FRS2 expression levels were increased in PDGF-BB-treated HA-VSMCs, and the miR-654-3p level was reduced. Moreover, circ_0007765 absence hindered PDGF-BB-induced HA-VSMC proliferation, invasion, and migration in vitro. At the molecular level, circ_0007765 increased FRS2 expression by acting as a sponge for miR-654-3p. Our findings revealed that circ_0007765 boosted PDGF-BB-induced HA-VSMC proliferation and migration through elevating FRS2 expression via adsorbing miR-654-3p, providing a feasible therapeutic strategy for AS.

Keywords: Atherosclerosis; FRS2; HA-VSMC; circ_0007765; miR-654-3p.

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Animals
  • Aorta / metabolism
  • Aorta / pathology
  • Atherosclerosis* / genetics
  • Atherosclerosis* / metabolism
  • Atherosclerosis* / pathology
  • Becaplermin* / pharmacology
  • Cell Movement* / drug effects
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Gene Expression Regulation
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Mice, Knockout, ApoE
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Muscle, Smooth, Vascular* / drug effects
  • Muscle, Smooth, Vascular* / metabolism
  • Muscle, Smooth, Vascular* / pathology
  • Myocytes, Smooth Muscle* / drug effects
  • Myocytes, Smooth Muscle* / metabolism
  • Myocytes, Smooth Muscle* / pathology
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism
  • Signal Transduction*

Substances

  • RNA, Circular
  • Becaplermin
  • MicroRNAs
  • FRS2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Membrane Proteins
  • Matrix Metalloproteinase 2