Circ_CHFR expedites cell growth, migration and inflammation in ox-LDL-treated human vascular smooth muscle cells via the miR-214-3p/Wnt3/β-catenin pathway

J.-B. Zhuang, T. Li, X.-M. Hu, M. Ning, W.-Q. Gao, Y.-H. Lang, W.-F. Zheng, J. Wei

Department of Cardiology, Tianjin Third Central Hospital, Tianjin Medical University, Tianjin, China. huaiyoujunjnqux@163.com

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• Cardiology

OBJECTIVE: Atherosclerosis (AS) is a representative inflammatory vascular disease. This study explored the molecular pathogenesis of AS based on circular RNA (circRNA), the checkpoint with forkhead-associated and ring-finger domains (circ_CHFR).

PATIENTS AND METHODS: The cell model of AS in vitro was established by stimulating human vascular smooth muscle cells (VSMCs) with oxidized low-density lipoprotein (ox-LDL). The RNA expression was measured by quantitative Real-time polymerase chain reaction (qRT-PCR). Cell viability and colony formation ability were separately evaluated using 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) and colony formation assay. Cell migration was assessed via the transwell assay. The inflammation injury was analyzed by enzyme-linked immunosorbent assay (ELISA). Associated proteins were determined through Western blot. The combination of hypothetic targets was ascertained using Dual-Luciferase reporter assay.

RESULTS: Circ_CHFR was up-regulated in AS serums and ox-LDL-stimulated VSMCs. Circ_CHFR depletion weakened the ox-LDL-induced promotion of cell growth, migration and inflammation in VSMCs. Circ_CHFR positively regulated Wnt3 expression and the downregulation of Wnt3 abrogated the ox-LDL-triggered injuries in VSMCs. Circ_CHFR functioned as the sponge of microRNA-214-3p (miR-214-3p) and miR-214-3p targeted Wnt3. Circ_CHFR regulated cell growth, migration and inflammation via regulating the expression of Wnt3 as a competitive endogenous RNA (ceRNA) of miR-214 in ox-LDL-treated VSMCs. Circ_CHFR/miR-214-3p axis mediated the Wnt3/β-catenin signal pathway.

CONCLUSIONS: Circ_CHFR contributed to the progression of AS through the miR-214-3p/Wnt3/β-catenin signals, which illuminated the molecular mechanism of AS and suggested circ_CHFR might be an index for AS treatment.

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