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Eur Rev Med Pharmacol Sci ; 24(6): 3282-3292, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32271446

RESUMO

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


Assuntos
Aterosclerose/patologia , Proteínas de Ciclo Celular/genética , Inflamação/patologia , Proteínas de Neoplasias/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Ubiquitina-Proteína Ligases/genética , Aterosclerose/genética , Movimento Celular/genética , Proliferação de Células/genética , Células Cultivadas , Progressão da Doença , Humanos , Inflamação/genética , Lipoproteínas LDL/administração & dosagem , MicroRNAs/genética , Músculo Liso Vascular/citologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/patologia , RNA Circular/genética , Proteína Wnt3/genética , beta Catenina/metabolismo
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