hsa_circ_0000218/hsa-miR-139-3p/SOX4 regulatory feedback circuit influences the proliferation and apoptosis of gastric cancer cells.

Previous studies have reported that circular (circ)RNAs serve an important role in cancer progression, but the effects of hsa_circRNA_0000218 (circ_0000218) and its potential underlying mechanism in gastric cancer (GC) are not completely understood. In the present study, dual luciferase reporter and RNA pull down assays were performed to detect the relationship between microRNA (miR)-139-3p and circ_0000218, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect circ_0000218, miR-139-3p and SRY-box transcription factor 4 (SOX4) mRNA expression levels in GC and GES-1 cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Western blotting was performed to assess cleaved-Caspase3 and Caspase3 expression levels in GC cells. circ_0000218 and SOX4 were highly expressed, whereas miR-139-3p was lowly expressed in GC cells. Moreover, circ_0000218 negatively regulated miR-139-3p in GC cells. circ_0000218 knockdown inhibited GC cell proliferation, promoted apoptosis and enhanced cleaved-Caspase3 expression in GC cells, whereas miR-139-3p knockdown reversed these effects. miR-139-3p overexpression inhibited proliferation and induced apoptosis in GC cells, but these effects were reversed by SOX4 overexpression. Collectively, the present study demonstrated that circ_0000218 upregulated SOX4 via downregulating miR-139-3p to promote GC progression.