Circ_0003356 suppresses gastric cancer growth through targeting the miR-668-3p/SOCS3 axis

BACKGROUND Circular RNAs(circRNAs)have attracted extensive attention as therapeutic targets in gastric cancer(GC).Circ_0003356 is known to be downregulated in GC tissues,but its cellular function and mechanisms remain undefined.AIM To investigate the role of circ_0003356 in GC at the molecular and cellular level.METHODS Circ_0003356,miR-668-3p,and SOCS3 expression were assessed via quantitative real time-polymerase chain reaction(qRT-PCR).Wound healing,EdU,CCK-8,flow cytometry and transwell assays were used to analyze the migration,proliferation,viability,apoptosis and invasion of GC cells.The subcellular localization of circ_0003356 was monitored using fluorescence in situ hybridization.The interaction of circ_0003356 with miR-668-3p was confirmed using RIP-qRT-PCR,RNA pull-down,and dual luciferase reporter assays.We observed protein levels of genes via western blot.We injected AGS cells into the upper back of mice and performed immunohistochemistry staining for examining E-cadherin,N-cadherin,Ki67,and SOCS3 expressions.TUNEL staining was performed for the assessment of apoptosis in mouse tumor tissues.RESULTS Circ_0003356 and SOCS3 expression was downregulated in GC cells,whilst miR-668-3p was upregulated.Exogenous circ_0003356 expression and miR-668-3p silencing suppressed the migration,viability,proliferation,epithelial to mesenchy-mal transition(EMT)and invasion of GC cells and enhanced apoptosis.Circ_0003356 overexpression impaired tumor growth in xenograft mice.Targeting of miR-668-3p by circ_0003356 was confirmed through binding assays and SOCS3 was identified as a downstream target of miR-668-3p.The impacts of circ_0003356 on cell proliferation,apoptosis,migration,invasion and EMT were reversed by miR-668-3p up-regulation or SOCS3 downregulation in GC cells.CONCLUSION Circ_0003356 impaired GC development through its interaction with the miR-668-3p/SOCS3 axis.