Circ_0002984 Enhances Growth, Invasion, and Migration in PDGF-bb–Induced Vascular Smooth Muscle Cells Through miR-379-5p/FRS2 Axis

Dec 9, 2021Journal of cardiovascular pharmacology

Circ_0002984 may increase growth, invasion, and movement of blood vessel muscle cells triggered by PDGF-bb through the miR-379-5p/FRS2 pathway

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Abstract

Circ_0002984 is elevated in human vascular smooth muscle cells (HVSMCs) induced by platelet-derived growth factor type bb (PDGF-bb).

Circ_0002984 knockdown reduced PDGF-bb-induced proliferation, migration, and invasion in HVSMCs.
Circ_0002984 targets microRNA (miR)-379-5p, which is associated with the regulation of HVSMC dysfunction.
Upregulation of miR-379-5p reversed the protective effects of circ_0002984 knockdown in HVSMCs.
FRS2 was identified as a target of miR-379-5p, and its overexpression mitigated the effects of miR-379-5p restoration.
Circ_0002984 may regulate FRS2 expression by sponging miR-379-5p in HVSMCs.

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The accumulation of vascular smooth muscle cells (VSMCs) is considered to play important roles in atherosclerosis (AS) development and progression. Circ_0002984 was found to be increased in oxidized low-density lipoprotein (ox-LDL) human VSMCs (HVSMCs). However, the function and mechanism of circ_0002984 in VSMC dysfunction remain unknown. In this study, the expression of circ_0002984, microRNA (miR)-379-5p, and fibroblast growth factor receptor substrate 2 (FRS2) was detected using quantitative real-time polymerase chain reaction and western blot. Cell proliferation, cell cycle, migration, and invasion were detected using Cell Counting Kit-8, flow cytometry, and transwell assays. The binding interaction between miR-379-5p and circ_0002984 or FRS2 was confirmed by the dual-luciferase reporter assay. Collectively, this study found that circ_0002984 was elevated in platelet-derived growth factor type bb (PDGF-bb)-induced HVSMCs. Circ_0002984 knockdown abrogated PDGF-bb-induced proliferation, migration, and invasion in HVSMCs. Mechanistically, circ_0002984 was confirmed to target miR-379-5p, and miR-379-5p upregulation reversed the protective effects of circ_0002984 knockdown on PDGF-bb-induced HVSMCs. Besides, when FRS2 was a target of miR-379-5p, miR-379-5p restoration abolished PDGF-bb-evoked HVSMC dysfunction, which was attenuated by the overexpression of FRS2. Moreover, circ_0002984 could regulate FRS2 expression through sponging miR-379-5p in HVSMCs. Collectively, these results demonstrated that circ_0002984 promoted PDGF-bb-induced VSMC proliferation, migration, and invasion through the regulation of miR-379-5p/FRS2 axis, suggesting a new insight into the pathogenesis of AS and the potential application of circ_0002984 in AS treatment.

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Circ_0002984 Enhances Growth, Invasion, and Migration in PDGF-bb–Induced Vascular Smooth Muscle Cells Through miR-379-5p/FRS2 Axis

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