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.