Published online May 15, 2023. doi: 10.4251/wjgo.v15.i5.787
Peer-review started: November 30, 2022
First decision: December 25, 2022
Revised: January 6, 2023
Accepted: April 7, 2023
Article in press: April 7, 2023
Published online: May 15, 2023
Processing time: 163 Days and 7.8 Hours
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.
To investigate the role of circ_0003356 in GC at the molecular and cellular level.
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.
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 mese
Circ_0003356 impaired GC development through its interaction with the miR-668-3p/SOCS3 axis.
Core Tip: We observed the low level of circ_0003356 expression in gastric cancer (GC) tissues and cells. Circ_0003356 expression was positively related to GC patient prognosis. Exogenous circ_0003356 overexpression and/or miR-668-3p suppression enhanced apoptosis in GC cells and suppressed GC cell proliferation, migration, invasion, and epithelial to mesenchy-mal transition. The overexpression of circ_0003356 also prevented tumor growth in mice. At the mechansistic level, circ_0003356 was found to interact with the miR-668-3p/SOCS3 axis to impair GC development. Together, we reveal new and important molecular details highlighting circ_0003356 as a novel cancer target.